Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) (CASPIAN)

• ClinicalTrials.gov Identifier: NCT03043872
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2017
• Results First Posted: March 4, 2021
• Last Update Posted: December 21, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Carcinoma Extensive Disease
• Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide
• Enrollment: 987

Participant Flow

Recruitment Details	Study was conducted in 209 study centers across 23 countries. It included a global cohort (805 patients) and China cohort (188 patients). China cohort comprised 6 patients also in the global cohort and a further 182 patients randomized after end of global cohort recruitment. Results of the global and China cohorts were reported separately.
Pre-assignment Details	Patients were randomized in a 1:1:1 ratio to receive treatment with durvalumab + tremelimumab + etoposide and platinum-based chemotherapy (EP), durvalumab + EP or EP alone. 987 participants were randomized in the study overall. Patients included in both cohorts for Started, Completed and Reasons for Not Completed are not double-counted for participant flow.

Arm/Group Title	All Patients: D + T + EP	All Patients: D + EP	All Patients: EP
Arm/Group Description	During Chemotherapy: Patients received durvalumab (D) 1500 milligrams (mg) in combination with tremelimumab (T) 75 mg intravenous (IV) infusion every 3 weeks (Q3W) for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/meters squared [m^2]) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion every 4 weeks (Q4W) from Week 12 until progressive disease (PD), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Period Title: Overall Study
Started [1]	329	328	330
Randomized and Included in Global Cohort Analysis	268	268	269
Received Treatment in Global Cohort	266	265	266
Randomized and Included in China Cohort Analysis	65	61	62
Received Treatment in China Cohort	65	61	62
Included in Both Cohorts (Global + China)	4	1	1
Ongoing Study at Global Cohort Final Analysis Data Cut-off (DCO)	56	56	31
Ongoing Study at China Cohort Second (Final) Analysis DCO	16	11	7
Completed [2]	51	52	18
Not Completed	278	276	312
Reason Not Completed
Withdrawal by Subject	6	6	15
Lost to Follow-up	2	1	1
Death	270	269	296
[1] Randomized in overall study; [2] Ongoing in overall study at long-term follow-up (LTFU) analysis DCO

Baseline Characteristics

Arm/Group Title		All Patients: D + T + EP	All Patients: D + EP	All Patients: EP	Total
Arm/Group Description		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.	Total of all reporting groups
Overall Number of Baseline Participants		329	328	330	987
Baseline Analysis Population Description		Baseline analysis was based on the global full analysis set (FAS) (all patients randomized prior to the end of global recruitment) plus the China FAS (all randomized patients in the China cohort). Patients included in both cohorts are not double-counted for the baseline analysis represented by 'All Patients'.
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Al Patients	Number Analyzed	329 participants	328 participants	330 participants	987 participants
	<50	21 6.4%	13 4.0%	28 8.5%	62 6.3%
	≥50 to <65	175 53.2%	195 59.5%	169 51.2%	539 54.6%
	≥65 to <75	108 32.8%	98 29.9%	110 33.3%	316 32.0%
	≥75	25 7.6%	22 6.7%	23 7.0%	70 7.1%
Global Cohort	Number Analyzed	268 participants	268 participants	269 participants	805 participants
	<50	16 6.0%	10 3.7%	20 7.4%	46 5.7%
	≥50 to <65	138 51.5%	157 58.6%	137 50.9%	432 53.7%
	≥65 to <75	91 34.0%	82 30.6%	90 33.5%	263 32.7%
	≥75	23 8.6%	19 7.1%	22 8.2%	64 8.0%
China Cohort	Number Analyzed	65 participants	61 participants	62 participants	188 participants
	<50	5 7.7%	3 4.9%	8 12.9%	16 8.5%
	≥50 to <65	40 61.5%	39 63.9%	33 53.2%	112 59.6%
	≥65 to <75	17 26.2%	16 26.2%	20 32.3%	53 28.2%
	≥75	3 4.6%	3 4.9%	1 1.6%	7 3.7%
		[1] Measure Analysis Population Description: Baseline data is presented for all patients, as well as separately for the global and China cohorts.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Patients	Number Analyzed	329 participants	328 participants	330 participants	987 participants
	Female	74 22.5%	86 26.2%	95 28.8%	255 25.8%
	Male	255 77.5%	242 73.8%	235 71.2%	732 74.2%
Global Cohort	Number Analyzed	268 participants	268 participants	269 participants	805 participants
	Female	66 24.6%	78 29.1%	85 31.6%	229 28.4%
	Male	202 75.4%	190 70.9%	184 68.4%	576 71.6%
China Cohort	Number Analyzed	65 participants	61 participants	62 participants	188 participants
	Female	8 12.3%	9 14.8%	10 16.1%	27 14.4%
	Male	57 87.7%	52 85.2%	52 83.9%	161 85.6%
		[1] Measure Analysis Population Description: Baseline data is presented for all patients, as well as separately for the global and China cohorts.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Patients	Number Analyzed	329 participants	328 participants	330 participants	987 participants
	Hispanic or Latino	7 2.1%	10 3.0%	6 1.8%	23 2.3%
	Not Hispanic or Latino	321 97.6%	315 96.0%	322 97.6%	958 97.1%
	Unknown or Not Reported	1 0.3%	3 0.9%	2 0.6%	6 0.6%
Global Cohort	Number Analyzed	268 participants	268 participants	269 participants	805 participants
	Hispanic or Latino	7 2.6%	10 3.7%	6 2.2%	23 2.9%
	Not Hispanic or Latino	260 97.0%	255 95.1%	261 97.0%	776 96.4%
	Unknown or Not Reported	1 0.4%	3 1.1%	2 0.7%	6 0.7%
China Cohort	Number Analyzed	65 participants	61 participants	62 participants	188 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	65 100.0%	61 100.0%	62 100.0%	188 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: Baseline data is presented for all patients, as well as separately for the global and China cohorts.
Race [1]; Measure Type: Count of Participants; Unit of measure: Participants
All Patients	Number Analyzed	329 participants	328 participants	330 participants	987 participants
	White	215 65.3%	229 69.8%	221 67.0%	665 67.4%
	Black or African American	1 0.3%	2 0.6%	3 0.9%	6 0.6%
	Asian	108 32.8%	96 29.3%	103 31.2%	307 31.1%
	Other	5 1.5%	1 0.3%	2 0.6%	8 0.8%
	Missing	0 0.0%	0 0.0%	1 0.3%	1 0.1%
Global Cohort	Number Analyzed	268 participants	268 participants	269 participants	805 participants
	White	215 80.2%	229 85.4%	221 82.2%	665 82.6%
	Black or African American	1 0.4%	2 0.7%	3 1.1%	6 0.7%
	Asian	47 17.5%	36 13.4%	42 15.6%	125 15.5%
	Other	5 1.9%	1 0.4%	2 0.7%	8 1.0%
	Missing	0 0.0%	0 0.0%	1 0.4%	1 0.1%
China Cohort	Number Analyzed	65 participants	61 participants	62 participants	188 participants
	White	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	65 100.0%	61 100.0%	62 100.0%	188 100.0%
	Other	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Missing	0 0.0%	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: Baseline data is presented for all patients, as well as separately for the global and China cohorts.

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP
Description	OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An interim analysis of OS in the global cohort was pre-specified after approximately 318 OS events occurred each between the D + EP and EP groups (60% maturity), and between the D + T + EP and EP groups (60% maturity). At the global cohort interim analysis DCO (11 March 2019), comparison of OS in the D + EP versus (vs) EP groups had crossed the pre-specified boundary. Since these results were considered final in terms of formal statistical testing, they are presented here as a primary outcome measure. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the global cohort final analysis is presented separately in the subsequent primary outcome measure.
Time Frame	From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. Interim analysis for OS in the global cohort was performed for comparison of the D + EP vs EP groups only.

Arm/Group Title	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	269
Median (95% Confidence Interval); Unit of Measure: months
	13.0; (11.5 to 14.8)	10.3; (9.3 to 11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + EP, Global Cohort: EP
	Comments	D + EP vs EP. The global cohort interim analysis of OS was based on a Lan-DeMets alpha spending function with O'Brien Fleming type boundary, using the actual number of events observed as a proportion of the planned total. Boundary for declaring statistical significance was 0.0178 for a 4% overall alpha. Hazard Ratio (HR) <1 favors D + EP to be associated with a longer OS than EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0047
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.591 to 0.909
	Estimation Comments	The HR and confidence intervals (CIs) were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

2. Primary Outcome

Title	OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP
Description	OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This primary outcome measure presents OS for the analysis of D + EP vs EP and D + T + EP vs EP at the time of the global cohort final analysis DCO (27 January 2020). Analysis of D + EP vs EP at the global cohort interim analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (global cohort final analysis) is presented as a secondary outcome measure.
Time Frame	From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	268	269
Median (95% Confidence Interval); Unit of Measure: months
	10.4; (9.6 to 12.0)	12.9; (11.3 to 14.7)	10.5; (9.3 to 11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + EP, Global Cohort: EP
	Comments	D + EP vs EP. HR <1 favors D + EP to be associated with a longer OS than EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0032
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.625 to 0.910
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + T + EP, Global Cohort: EP
	Comments	D + T + EP vs EP. The alpha level applied at the global cohort final analysis was adjusted (using a generalized Haybittle-Peto method) to account for actual alpha spent at the interim analysis based on the actual final total number of events, and thus maintain control of overall Type I error. Boundary for declaring statistical significance was 0.0418 for a 5% overall alpha. HR <1 favors D + T + EP to be associated with a longer OS than EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0451
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.682 to 0.995
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

3. Primary Outcome

Title	OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP
Description	OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure.
Time Frame	From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort. China cohort first analysis for OS was performed for comparison of the D + EP vs EP groups only.

Arm/Group Title	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	61	62
Median (95% Confidence Interval); Unit of Measure: months
	14.4 [1]; (12.3 to NA)	10.9; (8.9 to 14.0)

[1]

Upper limit of 95% CI could not be calculated as it was not reached.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + EP, China Cohort: EP
	Comments	D + EP vs EP. HR <1 favors D + EP to be associated with a longer OS than EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0664
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.414 to 1.029
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

4. Primary Outcome

Title	OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP
Description	OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure.
Time Frame	From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Median (95% Confidence Interval); Unit of Measure: months
	16.1; (11.3 to 18.6)	14.4; (12.3 to 17.0)	10.9; (8.9 to 14.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + EP, China Cohort: EP
	Comments	D + EP vs EP. HR <1 favors D + EP to be associated with a longer OS than EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1455
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.504 to 1.106
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + T + EP, China Cohort: EP
	Comments	D + T + EP vs EP. HR <1 favors D + T + EP to be associated with a longer OS than EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0314
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.439 to 0.964
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

5. Secondary Outcome

Title	OS in the Global Cohort; D + T + EP Compared With D + EP
Description	OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP in the global cohort. The alternative treatment comparisons in the global cohort were performed as primary outcome measures.
Time Frame	From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed	268	268
Median (95% Confidence Interval); Unit of Measure: months
	10.4; (9.6 to 12.0)	12.9; (11.3 to 14.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + T + EP, Global Cohort: D + EP
	Comments	D + T + EP vs D + EP. HR <1 favors D + T + EP to be associated with a longer OS than D + EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4352
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.890 to 1.309
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

6. Secondary Outcome

Title	Progression-Free Survival (PFS) in the Global Cohort
Description	PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 millimeters (mm) for the sum from nadir. For evaluation of non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	268	269
Median (95% Confidence Interval); Unit of Measure: months
	4.9; (4.7 to 5.9)	5.1; (4.7 to 6.2)	5.4; (4.8 to 6.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + EP, Global Cohort: EP
	Comments	D + EP vs EP. HR <1 favors D + EP to be associated with a longer PFS than EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0157
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.665 to 0.959
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + T + EP, Global Cohort: EP
	Comments	D + T + EP vs EP. HR <1 favors D + T + EP to be associated with a longer PFS than EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0568
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.696 to 1.005
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + T + EP, Global Cohort: D + EP
	Comments	D + T + EP vs D + EP. HR <1 favors D + T + EP to be associated with a longer PFS than D + EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7540
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.857 to 1.235
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

7. Secondary Outcome

Title	Objective Response Rate (ORR) in the Global Cohort
Description	ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of Complete Response (CR) or Partial Response (PR). CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. The denominator was a subset of the FAS population who had measurable disease at baseline.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	267	268	269
Measure Type: Number; Unit of Measure: percentage of patients
	74.2	79.5	70.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + EP, Global Cohort: EP
	Comments	D + EP vs EP. An odds ratio >1 favors D + EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0177
	Comments	Analysis was performed using a logistic regression model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin). P-value is based on twice the change in log-likelihood resulting from addition of a treatment factor to the model.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 1.086 to 2.401
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Global Cohort: D + T + EP, Global Cohort: EP
	Comments	D + T + EP vs EP. An odds ratio >1 favors D + T + EP.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3611
	Comments	Analysis was performed using a logistic regression model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin). P-value is based on twice the change in log-likelihood resulting from addition of a treatment factor to the model.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.817 to 1.746
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort
Description	The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	268	269
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	43.2; (37.1 to 49.1)	45.4; (39.3 to 51.3)	45.8; (39.5 to 51.9)

9. Secondary Outcome

Title	Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort
Description	The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	268	269
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	16.9; (12.6 to 21.7)	17.9; (13.5 to 22.8)	5.3; (2.9 to 8.8)

10. Secondary Outcome

Title	Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort
Description	OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.
Time Frame	At 18 months post-randomization. Assessed at the global cohort final analysis DCO (27 January 2020).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	268	268	269
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	30.7; (25.2 to 36.4)	32.0; (26.5 to 37.7)	24.8; (19.7 to 30.1)

11. Secondary Outcome

Title	Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort
Description	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame	Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Outcome Measure Data

Analysis Population Description

The global PK analysis set included all patients randomized prior to the end of global recruitment who received at least 1 dose of investigational product (IP), per the protocol for whom any post-dose PK data were available. PK for durvalumab was performed for the D + T + EP and D + EP groups only.

Arm/Group Title		Global Cohort: D + T + EP	Global Cohort: D + EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed		257	261
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms/milliliter (μg/mL)
Week 0: peak concentration	Number Analyzed	239 participants	226 participants
		447.3; (78.21%)	502.6; (30.52%)
Week 3: trough concentration	Number Analyzed	232 participants	237 participants
		91.86; (74.36%)	109.5; (64.55%)
Week 12: trough concentration	Number Analyzed	173 participants	200 participants
		199.2; (49.58%)	239.3; (50.68%)

12. Secondary Outcome

Title	PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort
Description	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame	Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Outcome Measure Data

Analysis Population Description

The global PK analysis set included all patients randomized prior to the end of global recruitment who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for tremelimumab was performed for the D + T + EP group only.

Arm/Group Title		Global Cohort: D + T + EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.
Overall Number of Participants Analyzed		257
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: μg/mL
Week 0: peak concentration	Number Analyzed	236 participants
		22.77; (52.15%)
Week 3: trough concentration	Number Analyzed	227 participants
		4.245; (81.68%)
Week 12: trough concentration	Number Analyzed	148 participants
		7.576; (59.25%)

13. Secondary Outcome

Title	Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort
Description	Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Outcome Measure Data

Analysis Population Description

The global ADA evaluable patients included those in the global safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for durvalumab was performed for the D + T + EP and D + EP groups only. The denominator was durvalumab ADA evaluable patients.

Arm/Group Title	Global Cohort: D + T + EP	Global Cohort: D + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed	191	205
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	6 3.1%	11 5.4%
Treatment-emergent ADA positive (ADA incidence)	0 0.0%	0 0.0%
Treatment-boosted ADA	0 0.0%	0 0.0%
Treatment-induced ADA (ADA positive post-baseline only)	0 0.0%	0 0.0%
ADA positive at baseline only	6 3.1%	11 5.4%
ADA positive post-baseline and positive at baseline	0 0.0%	0 0.0%
Persistently positive	0 0.0%	0 0.0%
Transiently positive	0 0.0%	0 0.0%
nAb positive at any visit	1 0.5%	0 0.0%

14. Secondary Outcome

Title	Number of Patients With ADA Response to Tremelimumab in the Global Cohort
Description	Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Outcome Measure Data

Analysis Population Description

The global ADA evaluable patients included those in the global safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for tremelimumab was performed for the D + T + EP group only. The denominator was tremelimumab ADA evaluable patients.

Arm/Group Title	Global Cohort: D + T + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.
Overall Number of Participants Analyzed	178
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	11 6.2%
Treatment-emergent ADA positive (ADA incidence)	5 2.8%
Treatment-boosted ADA	0 0.0%
Treatment-induced ADA (ADA positive post-baseline only)	5 2.8%
ADA positive at baseline only	6 3.4%
ADA positive post-baseline and positive at baseline	0 0.0%
Persistently positive	4 2.2%
Transiently positive	1 0.6%
nAb positive at any visit	2 1.1%

15. Secondary Outcome

Title	Time to Deterioration of Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) in the Global Cohort
Description	The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. For QLQ-C30 function scales and global health status/HRQoL, only patients with baseline scores ≥10 (and with data available) were included in the analysis. For QLQ-C30 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

Arm/Group Title		Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		262	261	260
Median (95% Confidence Interval); Unit of Measure: months
QLQ-C30 Global Health Status / HRQoL	Number Analyzed	247 participants	239 participants	232 participants
		7.2; (5.8 to 8.3)	8.4; (7.3 to 11.0)	7.4; (6.5 to 9.3)
QLQ-C30 Cognitive Functioning	Number Analyzed	251 participants	245 participants	242 participants
		6.0; (5.0 to 7.0)	8.4; (7.3 to 10.3)	6.0; (5.2 to 7.1)
QLQ-C30 Emotional Functioning	Number Analyzed	248 participants	242 participants	240 participants
		7.6; (6.6 to 9.5)	11.8; (8.6 to 16.6)	7.3; (6.7 to 8.3)
QLQ-C30 Physical Functioning	Number Analyzed	247 participants	244 participants	240 participants
		6.0; (5.0 to 6.9)	8.4; (7.4 to 12.0)	6.5; (6.0 to 8.2)
QLQ-C30 Role Functioning	Number Analyzed	236 participants	231 participants	226 participants
		5.0; (4.1 to 6.5)	7.4; (5.7 to 10.2)	5.9; (4.5 to 6.7)
QLQ-C30 Social Functioning	Number Analyzed	244 participants	237 participants	236 participants
		6.2; (5.0 to 7.4)	7.4; (6.5 to 8.8)	6.3; (4.9 to 7.4)
QLQ-C30 Fatigue	Number Analyzed	242 participants	244 participants	232 participants
		4.2; (3.1 to 4.7)	5.5; (4.0 to 6.6)	4.5; (3.5 to 5.3)
QLQ-C30 Nausea / Vomiting	Number Analyzed	252 participants	245 participants	244 participants
		7.5; (6.1 to 8.6)	8.4; (6.6 to 10.2)	6.6; (5.6 to 7.5)
QLQ-C30 Pain	Number Analyzed	243 participants	240 participants	233 participants
		6.9; (6.0 to 7.7)	8.0; (6.8 to 10.4)	6.7; (6.2 to 7.8)
QLQ-C30 Appetite Loss	Number Analyzed	236 participants	231 participants	224 participants
		6.9; (5.6 to 8.5)	8.3; (6.8 to 11.0)	6.6; (5.5 to 7.5)
QLQ-C30 Constipation	Number Analyzed	243 participants	240 participants	229 participants
		8.5; (7.1 to 10.8)	11.5; (8.3 to 14.7)	7.3; (6.2 to 9.0)
QLQ-C30 Diarrhea	Number Analyzed	250 participants	244 participants	244 participants
		8.9; (7.5 to 10.8)	14.7; (9.4 to 21.1)	7.7; (7.1 to 9.5)
QLQ-C30 Dyspnea	Number Analyzed	227 participants	225 participants	218 participants
		7.2; (5.6 to 8.3)	9.0; (7.6 to 12.7)	7.5; (6.6 to 9.0)
QLQ-C30 Insomnia	Number Analyzed	226 participants	226 participants	210 participants
		7.1; (6.1 to 8.6)	8.6; (7.1 to 11.8)	7.3; (6.4 to 8.3)

16. Secondary Outcome

Title	Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort
Description	The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. For QLQ-L13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

Arm/Group Title		Global Cohort: D + T + EP	Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		262	261	260
Median (95% Confidence Interval); Unit of Measure: months
QLQ-LC13 Coughing	Number Analyzed	233 participants	230 participants	230 participants
		7.7; (6.9 to 10.8)	9.3; (8.0 to 14.1)	7.7; (6.7 to 9.5)
QLQ-LC13 Dyspnea	Number Analyzed	249 participants	241 participants	240 participants
		6.3; (4.9 to 7.4)	6.5; (5.5 to 7.8)	5.5; (4.6 to 7.2)
QLQ-LC13 Hemoptysis	Number Analyzed	252 participants	243 participants	245 participants
		11.4; (8.9 to 18.6)	18.3 [1]; (14.5 to NA)	10.8; (8.4 to 11.9)
QLQ-LC13 Pain in Arm or Shoulder	Number Analyzed	245 participants	241 participants	238 participants
		7.1; (6.3 to 8.3)	9.7; (8.1 to 15.1)	7.6; (6.6 to 9.3)
QLQ-LC13 Pain in Chest	Number Analyzed	243 participants	239 participants	240 participants
		8.5; (7.2 to 10.8)	11.5; (8.4 to 15.8)	7.9; (7.2 to 9.9)
QLQ-LC13 Pain in Other Parts	Number Analyzed	245 participants	236 participants	231 participants
		7.4; (6.5 to 8.7)	7.8; (6.6 to 9.3)	6.6; (5.1 to 7.5)

[1]

Upper limit of 95% CI could not be calculated as it was not reached.

17. Secondary Outcome

Title	Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP
Description	A mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs P. Analysis of D + EP vs EP is presented in a separate outcome measure.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. For each symptom scale, only patients with data available were included in the analysis.

Arm/Group Title		Global Cohort: D + T + EP	Global Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		262	260
Mean (Standard Error); Unit of Measure: scores on a scale
EORTC QLQ-LC13 Cough	Number Analyzed	239 participants	232 participants
		-15.1 (1.74)	-14.6 (1.76)
EORTC QLQ-LC13 Dyspnea	Number Analyzed	239 participants	232 participants
		-6.8 (1.60)	-6.6 (1.62)
EORTC QLQ-LC13 Chest pain	Number Analyzed	239 participants	232 participants
		-7.4 (1.65)	-7.0 (1.67)
EORTC QLQ-C30 Fatigue	Number Analyzed	239 participants	233 participants
		-6.1 (1.84)	-6.3 (1.86)
EORTC QLQ-C30 Appetite loss	Number Analyzed	239 participants	233 participants
		-8.7 (2.02)	-9.5 (2.05)

18. Secondary Outcome

Title	Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP
Description	A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Outcome Measure Data

Analysis Population Description

The global FAS included all patients randomized prior to the end of global recruitment. For each symptom scale, only patients with data available were included in the analysis.

Arm/Group Title		Global Cohort: D + EP	Global Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		261	260
Mean (Standard Error); Unit of Measure: scores on a scale
EORTC QLQ-LC13 Cough	Number Analyzed	232 participants	232 participants
		-15.0 (1.64)	-15.4 (1.72)
EORTC QLQ-LC13 Dyspnea	Number Analyzed	232 participants	232 participants
		-7.1 (1.44)	-6.5 (1.50)
EORTC QLQ-LC13 Chest pain	Number Analyzed	232 participants	232 participants
		-7.8 (1.59)	-7.2 (1.65)
EORTC QLQ-C30 Fatigue	Number Analyzed	233 participants	233 participants
		-5.8 (1.62)	-4.5 (1.69)
EORTC QLQ-C30 Appetite loss	Number Analyzed	233 participants	233 participants
		-10.1 (1.73)	-7.6 (1.81)

19. Secondary Outcome

Title	OS in the China Cohort; D + T + EP Compared With D + EP
Description	OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP at the China cohort second analysis DCO (02 November 2020). The alternative treatment comparisons were performed as primary outcome measures.
Time Frame	From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed	65	61
Median (95% Confidence Interval); Unit of Measure: months
	16.1; (11.3 to 18.6)	14.4; (12.3 to 17.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + T + EP, China Cohort: D + EP
	Comments	D + T + EP vs D + EP. HR <1 favors D + T + EP to be associated with a longer OS than D + EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4470
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.574 to 1.277
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

20. Secondary Outcome

Title	PFS in the China Cohort
Description	PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 mm for the sum from nadir. For evaluation of NTLs, PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (4.8 to 6.6)	4.9; (4.7 to 5.5)	5.5; (4.9 to 6.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + EP, China Cohort: EP
	Comments	D + EP vs EP. HR <1 favors D + EP to be associated with a longer PFS than EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8934
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.661 to 1.437
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + T + EP, China Cohort: EP
	Comments	D + T + EP vs EP. HR <1 favors D + T + EP to be associated with a longer PFS than EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1035
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.487 to 1.068
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + T + EP, China Cohort: D + EP
	Comments	D + T + EP vs D + EP. HR <1 favors D + T + EP to be associated with a longer PFS than D + EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1673
	Comments	Analysis was performed using the stratified log-rank test, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and using the rank tests of association approach.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.522 to 1.116
	Estimation Comments	The HR and CIs were calculated using a stratified Cox proportional hazards model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin), and ties handled by Efron approach.

21. Secondary Outcome

Title	ORR in the China Cohort
Description	ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Measure Type: Number; Unit of Measure: percentage of patients
	84.6	78.7	72.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + EP, China Cohort: EP
	Comments	D + EP vs EP. An odds ratio >1 favors D + EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4320
	Comments	Analysis was performed using a logistic regression model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin). P-value is based on twice the change in log-likelihood resulting from addition of a treatment factor to the model.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; 0.610 to 3.244
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	China Cohort: D + T + EP, China Cohort: EP
	Comments	D + T + EP vs EP. An odds ratio >1 favors D + T + EP. The study was not designed or powered to show statistical significance for efficacy endpoints in the China cohort, so all statistical analyses for the China cohort were considered exploratory.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0986
	Comments	Analysis was performed using a logistic regression model, adjusting for planned platinum therapy in Cycle 1 (carboplatin or cisplatin). P-value is based on twice the change in log-likelihood resulting from addition of a treatment factor to the model.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.07
	Confidence Interval	(2-Sided) 95%; 0.874 to 5.118
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	APF6 in the China Cohort
Description	The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	43.7; (31.2 to 55.5)	35.2; (23.3 to 47.4)	43.1; (29.8 to 55.7)

23. Secondary Outcome

Title	APF12 in the China Cohort
Description	The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	21.0; (12.0 to 31.9)	12.3; (5.4 to 22.2)	6.2; (1.6 to 15.3)

24. Secondary Outcome

Title	OS18 in the China Cohort
Description	OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.
Time Frame	At 18 months post-randomization. Assessed at the China cohort second analysis DCO (02 November 2020).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed	65	61	62
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	40.0; (28.1 to 51.6)	36.1; (24.3 to 48.0)	23.4; (13.6 to 34.6)

25. Secondary Outcome

Title	PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort
Description	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame	Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Outcome Measure Data

Analysis Population Description

The China PK analysis set included all patients in the China cohort who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for durvalumab was performed for the D + T + EP and D + EP groups only.

Arm/Group Title		China Cohort: D + T + EP	China Cohort: D + EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed		64	59
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: μg/mL
Week 0: peak concentration	Number Analyzed	64 participants	59 participants
		429.4; (19.49%)	432.0; (91.79%)
Week 3: trough concentration	Number Analyzed	61 participants	54 participants
		81.21; (46.14%)	96.24; (64.44%)
Week 12: trough concentration	Number Analyzed	46 participants	50 participants
		151.0; (29.82%)	194.4; (53.34%)

26. Secondary Outcome

Title	PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort
Description	To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame	Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Outcome Measure Data

Analysis Population Description

The China PK analysis set included all patients in the China cohort who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for tremelimumab was performed for the D + T + EP group only.

Arm/Group Title		China Cohort: D + T + EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.
Overall Number of Participants Analyzed		64
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: μg/mL
Week 0: peak concentration	Number Analyzed	64 participants
		24.34; (27.05%)
Week 3: trough concentration	Number Analyzed	61 participants
		4.530; (60.60%)
Week 12: trough concentration	Number Analyzed	45 participants
		9.523; (43.94%)

27. Secondary Outcome

Title	Number of Patients With ADA Response to Durvalumab in the China Cohort
Description	Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Outcome Measure Data

Analysis Population Description

The China ADA evaluable patients included those in the China safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for durvalumab was performed for the D + T + EP and D + EP groups only. The denominator was durvalumab ADA evaluable patients.

Arm/Group Title	China Cohort: D + T + EP	China Cohort: D + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Overall Number of Participants Analyzed	53	51
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	0 0.0%	0 0.0%
Treatment-emergent ADA positive (ADA incidence)	0 0.0%	0 0.0%
Treatment-boosted ADA	0 0.0%	0 0.0%
Treatment-induced ADA (ADA positive post-baseline only)	0 0.0%	0 0.0%
ADA positive at baseline only	0 0.0%	0 0.0%
ADA positive post-baseline and positive at baseline	0 0.0%	0 0.0%
Persistently positive	0 0.0%	0 0.0%
Transiently positive	0 0.0%	0 0.0%
nAb positive at any visit	0 0.0%	0 0.0%

28. Secondary Outcome

Title	Number of Patients With ADA Response to Tremelimumab in the China Cohort
Description	Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Outcome Measure Data

Analysis Population Description

The China ADA evaluable patients included those in the China safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for tremelimumab was performed for the D + T + EP group only. The denominator was tremelimumab ADA evaluable patients.

Arm/Group Title	China Cohort: D + T + EP
Arm/Group Description:	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.
Overall Number of Participants Analyzed	51
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	3 5.9%
Treatment-emergent ADA positive (ADA incidence)	3 5.9%
Treatment-boosted ADA	0 0.0%
Treatment-induced ADA (ADA positive post-baseline only)	3 5.9%
ADA positive at baseline only	0 0.0%
ADA positive post-baseline and positive at baseline	0 0.0%
Persistently positive	3 5.9%
Transiently positive	0 0.0%
nAb positive at any visit	0 0.0%

29. Secondary Outcome

Title	Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort
Description	The EORTC QLQ-C30 v3 was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort. For QLQ-C30 function scales and global health status/HRQoL, only patients with baseline scores ≥10 (and with data available) were included in the analysis. For QLQ-C30 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

Arm/Group Title		China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		65	61	62
Median (95% Confidence Interval); Unit of Measure: months
QLQ-C30 Global Health Status / HRQoL	Number Analyzed	60 participants	57 participants	55 participants
		14.5 [1]; (6.8 to NA)	15.1 [1]; (7.6 to NA)	7.8; (6.5 to 10.9)
QLQ-C30 Cognitive Functioning	Number Analyzed	60 participants	58 participants	58 participants
		7.6 [1]; (4.9 to NA)	6.8 [1]; (2.3 to NA)	6.9 [1]; (5.7 to NA)
QLQ-C30 Emotional Functioning	Number Analyzed	60 participants	58 participants	58 participants
		20.4 [1]; (6.8 to NA)	15.5 [1]; (5.8 to NA)	10.0 [1]; (6.9 to NA)
QLQ-C30 Physical Functioning	Number Analyzed	60 participants	58 participants	58 participants
		21.8 [1]; (6.0 to NA)	9.3 [1]; (5.8 to NA)	7.3; (5.7 to 10.9)
QLQ-C30 Role Functioning	Number Analyzed	60 participants	56 participants	57 participants
		6.8; (4.9 to 21.3)	6.4; (4.2 to 13.9)	6.2; (4.1 to 10.0)
QLQ-C30 Social Functioning	Number Analyzed	60 participants	57 participants	56 participants
		6.7; (4.3 to 14.1)	5.8; (3.9 to 13.3)	6.5; (3.3 to 8.3)
QLQ-C30 Fatigue	Number Analyzed	60 participants	58 participants	58 participants
		3.7; (2.3 to 6.8)	5.3; (2.9 to 9.6)	3.9; (2.2 to 5.9)
QLQ-C30 Nausea / Vomiting	Number Analyzed	59 participants	58 participants	58 participants
		8.4 [1]; (4.7 to NA)	9.3; (3.9 to 15.5)	8.2; (5.7 to 10.9)
QLQ-C30 Pain	Number Analyzed	60 participants	57 participants	58 participants
		6.6; (4.9 to 17.3)	6.2; (5.5 to 15.1)	6.5; (4.6 to 8.6)
QLQ-C30 Appetite Loss	Number Analyzed	59 participants	57 participants	57 participants
		8.4 [1]; (2.6 to NA)	5.8 [1]; (3.3 to NA)	6.9; (5.7 to 10.0)
QLQ-C30 Constipation	Number Analyzed	59 participants	58 participants	58 participants
		NA [2]; (6.8 to NA)	12.0 [1]; (5.8 to NA)	10.9 [1]; (8.6 to NA)
QLQ-C30 Diarrhea	Number Analyzed	59 participants	58 participants	58 participants
		17.3 [1]; (9.8 to NA)	NA [1]; (13.3 to NA)	10.1 [1]; (8.2 to NA)
QLQ-C30 Dyspnea	Number Analyzed	60 participants	57 participants	56 participants
		11.6 [1]; (6.0 to NA)	15.5 [1]; (9.3 to NA)	7.3; (5.7 to 10.9)
QLQ-C30 Insomnia	Number Analyzed	60 participants	57 participants	58 participants
		7.3 [1]; (5.2 to NA)	15.5 [1]; (5.6 to NA)	7.8; (6.3 to 10.9)

[1]

Upper limit of 95% CI could not be calculated as it was not reached.

[2]

Median and upper limit of 95% CI could not be calculated as they were not reached.

30. Secondary Outcome

Title	Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort
Description	The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort. For QLQ-L13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

Arm/Group Title		China Cohort: D + T + EP	China Cohort: D + EP	China Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		65	61	62
Median (95% Confidence Interval); Unit of Measure: months
QLQ-LC13 Coughing	Number Analyzed	58 participants	56 participants	54 participants
		NA [1]; (6.8 to NA)	15.5 [2]; (5.8 to NA)	8.6 [2]; (6.8 to NA)
QLQ-LC13 Dyspnea	Number Analyzed	60 participants	58 participants	58 participants
		6.9 [2]; (3.4 to NA)	8.1; (5.3 to 15.5)	4.7; (2.5 to 8.6)
QLQ-LC13 Hemoptysis	Number Analyzed	60 participants	58 participants	58 participants
		NA [1]; (17.3 to NA)	NA [1]; (11.2 to NA)	10.1 [2]; (6.9 to NA)
QLQ-LC13 Pain in Arm or Shoulder	Number Analyzed	60 participants	55 participants	58 participants
		NA [1]; (6.9 to NA)	15.5 [2]; (5.6 to NA)	8.6; (6.3 to 10.9)
QLQ-LC13 Pain in Chest	Number Analyzed	59 participants	55 participants	57 participants
		NA [1]; (6.8 to NA)	15.5 [2]; (6.8 to NA)	10.0 [2]; (6.9 to NA)
QLQ-LC13 Pain in Other Parts	Number Analyzed	60 participants	58 participants	57 participants
		NA [1]; (7.0 to NA)	9.3 [2]; (6.2 to NA)	8.6; (5.7 to 10.9)

[1]

Median and upper limit of 95% CI could not be calculated as they were not reached.

[2]

Upper limit of 95% CI could not be calculated as it was not reached.

31. Secondary Outcome

Title	Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP
Description	A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs EP. Analysis of D + EP vs EP is presented in a separate outcome measure.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort. For each symptom scale, only patients with data available were included in the analysis.

Arm/Group Title		China Cohort: D + T + EP	China Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		65	62
Mean (Standard Error); Unit of Measure: scores on a scale
EORTC QLQ-LC13 Cough	Number Analyzed	60 participants	56 participants
		-12.8 (2.49)	-12.9 (2.50)
EORTC QLQ-LC13 Dyspnea	Number Analyzed	60 participants	56 participants
		-3.6 (2.21)	-0.8 (2.17)
EORTC QLQ-LC13 Chest pain	Number Analyzed	60 participants	56 participants
		-5.1 (2.16)	-5.4 (2.16)
EORTC QLQ-C30 Fatigue	Number Analyzed	60 participants	56 participants
		2.8 (2.10)	2.9 (2.11)
EORTC QLQ-C30 Appetite loss	Number Analyzed	60 participants	56 participants
		3.0 (2.36)	0.8 (2.42)

32. Secondary Outcome

Title	Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP
Description	A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure.
Time Frame	At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Outcome Measure Data

Analysis Population Description

The China FAS included all randomized patients in the China cohort. For each symptom scale, only patients with data available were included in the analysis.

Arm/Group Title		China Cohort: D + EP	China Cohort: EP
Arm/Group Description:		During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
Overall Number of Participants Analyzed		61	62
Mean (Standard Error); Unit of Measure: scores on a scale
EORTC QLQ-LC13 Cough	Number Analyzed	58 participants	56 participants
		-14.9 (2.66)	-16.7 (2.68)
EORTC QLQ-LC13 Dyspnea	Number Analyzed	58 participants	56 participants
		-2.2 (1.93)	-3.0 (1.97)
EORTC QLQ-LC13 Chest pain	Number Analyzed	58 participants	56 participants
		-6.7 (1.93)	-7.7 (1.95)
EORTC QLQ-C30 Fatigue	Number Analyzed	58 participants	56 participants
		1.5 (2.06)	0.8 (2.11)
EORTC QLQ-C30 Appetite loss	Number Analyzed	58 participants	56 participants
		3.6 (2.47)	-2.2 (2.51)

Adverse Events

Time Frame	All treatment-emergent adverse events (TEAEs) were collected up to the final analysis DCO for each cohort; maximum of approximately 33 months for the Global cohort and maximum of approximately 29 months for the China cohort. Serious AEs and Deaths were collected through LTFU analysis in patients still receiving durvalumab (or within 90 days of discontinuing treatment); up to approximately 4 years.
Adverse Event Reporting Description	TEAEs included those from first administration of study treatment up to and including 90 days after last dose of study treatment or up to date of initiation of the first subsequent anticancer therapy (whichever occurred first). Data from the global cohort and China cohort safety analysis sets was summarised separately. 6 patients in the China cohort were also included in the global cohort.
Arm/Group Title	Global Cohort: D + T + EP		Global Cohort: D + EP		Global Cohort: EP		China Cohort: D + T + EP		China Cohort: D + EP		China Cohort: EP
Arm/Group Description	During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.		During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.		For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.		During Chemotherapy: Patients received durvalumab (D) 1500 mg in combination with tremelimumab (T) 75 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg IV infusion post-chemotherapy (in combination with durvalumab) at Week 16 if they completed all 4 doses of durvalumab + tremelimumab during chemotherapy.		During Chemotherapy: Patients received durvalumab (D) 1500 mg IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Post-Chemotherapy: Patients then continued to receive durvalumab 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.		For chemotherapy (EP), patients received etoposide (80-100 mg/m^2) with either carboplatin (area under the curve 5-6) or cisplatin (75-80 mg/m^2) IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). An additional 2 doses of EP (at Weeks 12 and 15) could be given at the investigators' discretion if clinically indicated.
All-Cause Mortality
	Global Cohort: D + T + EP		Global Cohort: D + EP		Global Cohort: EP		China Cohort: D + T + EP		China Cohort: D + EP		China Cohort: EP
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	225/266 (84.59%)		218/265 (82.26%)		247/266 (92.86%)		50/65 (76.92%)		51/61 (83.61%)		55/62 (88.71%)
Serious Adverse Events
	Global Cohort: D + T + EP		Global Cohort: D + EP		Global Cohort: EP		China Cohort: D + T + EP		China Cohort: D + EP		China Cohort: EP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	126/266 (47.37%)		86/265 (32.45%)		97/266 (36.47%)		31/65 (47.69%)		26/61 (42.62%)		22/62 (35.48%)
Blood and lymphatic system disorders
Anaemia † 1	9/266 (3.38%)	11	5/265 (1.89%)	8	12/266 (4.51%)	14	2/65 (3.08%)	2	0/61 (0.00%)	0	2/62 (3.23%)	2
Bone marrow failure † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	5/65 (7.69%)	5	6/61 (9.84%)	6	7/62 (11.29%)	11
Febrile neutropenia † 1	11/266 (4.14%)	12	12/265 (4.53%)	15	12/266 (4.51%)	13	2/65 (3.08%)	3	0/61 (0.00%)	0	0/62 (0.00%)	0
Granulocytopenia † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Haematotoxicity † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Leukopenia † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	2/62 (3.23%)	2
Neutropenia † 1	5/266 (1.88%)	5	2/265 (0.75%)	2	7/266 (2.63%)	12	0/65 (0.00%)	0	1/61 (1.64%)	1	3/62 (4.84%)	3
Pancytopenia † 1	2/266 (0.75%)	3	4/265 (1.51%)	4	3/266 (1.13%)	3	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Thrombocytopenia † 1	6/266 (2.26%)	6	1/265 (0.38%)	1	9/266 (3.38%)	11	3/65 (4.62%)	3	0/61 (0.00%)	0	1/62 (1.61%)	1
Cardiac disorders
Acute myocardial infarction † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	2/266 (0.75%)	2	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Angina unstable † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Atrial fibrillation † 1	3/266 (1.13%)	3	2/265 (0.75%)	2	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Cardiac arrest † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cardiac dysfunction † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cardiac failure † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	2/61 (3.28%)	2	0/62 (0.00%)	0
Cardiac failure acute † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cardiac failure chronic † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cardiopulmonary failure † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Left ventricular failure † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Myocardial infarction † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Myocardial ischaemia † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Myocarditis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Pericardial effusion † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Hyperthyroidism † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypoparathyroidism † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypopituitarism † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypothyroidism † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Inappropriate antidiuretic hormone secretion † 1	5/266 (1.88%)	5	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Secondary adrenocortical insufficiency † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Eye disorders
Angle closure glaucoma † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Retinal detachment † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Retinopathy † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Vitreous detachment † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Abdominal pain † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Acute abdomen † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Constipation † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Enteritis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	2	1/61 (1.64%)	1	0/62 (0.00%)	0
Enterocolitis † 1	4/266 (1.50%)	4	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Food poisoning † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Gastritis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Haematemesis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Ileus † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Large intestinal haemorrhage † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Large intestinal obstruction † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Nausea † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	2/266 (0.75%)	2	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Oesophageal obstruction † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Stomatitis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Vomiting † 1	3/266 (1.13%)	3	0/265 (0.00%)	0	3/266 (1.13%)	3	0/65 (0.00%)	0	1/61 (1.64%)	1	1/62 (1.61%)	1
Colitis † 1	5/266 (1.88%)	6	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Diarrhoea † 1	7/266 (2.63%)	7	2/265 (0.75%)	2	4/266 (1.50%)	4	2/65 (3.08%)	2	0/61 (0.00%)	0	0/62 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Pancreatitis acute † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
General disorders
Asthenia † 1	1/266 (0.38%)	1	1/265 (0.38%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	2/62 (3.23%)	2
Chest pain † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Condition aggravated † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Death † 1	4/266 (1.50%)	4	0/265 (0.00%)	0	2/266 (0.75%)	2	1/65 (1.54%)	1	2/61 (3.28%)	2	2/62 (3.23%)	2
Drowning † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Malaise † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	1/62 (1.61%)	1
Mucosal inflammation † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Multiple organ dysfunction syndrome † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
General physical health deterioration † 1	1/266 (0.38%)	1	2/265 (0.75%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Oedema peripheral † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pain † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pyrexia † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	2/266 (0.75%)	2	0/65 (0.00%)	0	2/61 (3.28%)	2	0/62 (0.00%)	0
Sudden cardiac death † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Sudden death † 1	2/266 (0.75%)	2	2/265 (0.75%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hepatobiliary disorders
Cholangitis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cholecystitis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cholecystitis acute † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Drug-induced liver injury † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Hepatic failure † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hepatic function abnormal † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Hepatitis † 1	3/266 (1.13%)	3	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hepatotoxicity † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hyperbilirubinaemia † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Immune-mediated hepatitis † 1	2/266 (0.75%)	3	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Contrast media allergy † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Drug hypersensitivity † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypersensitivity † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Infections and infestations
Abdominal sepsis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Anal abscess † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Bacterial prostatitis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Bronchitis † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Clostridium difficile colitis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cystitis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Device related sepsis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Diverticulitis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Gastroenteritis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Hepatitis C † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Herpes zoster † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Infection † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Infectious pleural effusion † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Influenza † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Kidney infection † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Lower respiratory tract infection † 1	3/266 (1.13%)	4	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Lung abscess † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pneumocystis jirovecii pneumonia † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pneumonia † 1	16/266 (6.02%)	17	6/265 (2.26%)	6	11/266 (4.14%)	12	9/65 (13.85%)	9	5/61 (8.20%)	5	2/62 (3.23%)	2
Pneumonia bacterial † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pyelonephritis acute † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Respiratory tract infection † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Sepsis † 1	0/266 (0.00%)	0	3/265 (1.13%)	3	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Septic shock † 1	0/266 (0.00%)	0	3/265 (1.13%)	3	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Systemic candida † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Upper respiratory tract infection † 1	1/266 (0.38%)	1	2/265 (0.75%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Urinary tract infection † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Urinary tract infection bacterial † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Urinary tract infection pseudomonal † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Vascular device infection † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Viral infection † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Injury, poisoning and procedural complications
Accidental exposure to product † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Craniocerebral injury † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Fall † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Femur fracture † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hip fracture † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Injury † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Lumbar vertebral fracture † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Meniscus injury † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Radiation pneumonitis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Spinal compression fracture † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Toxicity to various agents † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Investigations
Blood creatinine increased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	1/61 (1.64%)	1	0/62 (0.00%)	0
Body temperature increased † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
C-reactive protein increased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Influenza B virus test positive † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Lipase increased † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Liver function test increased † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Neutrophil count decreased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	1/61 (1.64%)	1	1/62 (1.61%)	1
Platelet count decreased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	2/65 (3.08%)	2	0/61 (0.00%)	0	1/62 (1.61%)	2
Transaminases increased † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
White blood cell count decreased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	2/61 (3.28%)	2	1/62 (1.61%)	1
Dehydration † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Diabetes mellitus † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Diabetes mellitus inadequate control † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Diabetic ketoacidosis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Diabetic ketosis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Diabetic metabolic decompensation † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Electrolyte imbalance † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypercalcaemia † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hyperglycaemia † 1	3/266 (1.13%)	3	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hyperkalaemia † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	1/266 (0.38%)	1	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Hyperuricaemia † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypocalcaemia † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Hypokalaemia † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	3/266 (1.13%)	3	0/65 (0.00%)	0	0/61 (0.00%)	0	2/62 (3.23%)	2
Hyponatraemia † 1	9/266 (3.38%)	10	2/265 (0.75%)	2	4/266 (1.50%)	5	1/65 (1.54%)	1	2/61 (3.28%)	2	2/62 (3.23%)	2
Ketoacidosis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Tumour lysis syndrome † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Type 1 diabetes mellitus † 1	1/266 (0.38%)	1	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Back pain † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	2/61 (3.28%)	2	0/62 (0.00%)	0
Bone pain † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Muscle spasms † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Muscular weakness † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Musculoskeletal chest pain † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Myalgia † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Osteonecrosis of jaw † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Clear cell renal cell carcinoma † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Invasive ductal breast carcinoma † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Laryngeal cancer † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Metastases to bone † 1	0/266 (0.00%)	0	1/265 (0.38%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Non-Hodgkin's lymphoma † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pancreatic carcinoma † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Rectal cancer † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Small intestine leiomyosarcoma † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Tumour associated fever † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Nervous system disorders
Altered state of consciousness † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Brain oedema † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cerebral haemorrhage † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cerebral ischaemia † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cerebrovascular accident † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	3/266 (1.13%)	3	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Cerebrovascular insufficiency † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Encephalopathy † 1	2/266 (0.75%)	3	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Haemorrhage intracranial † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Ischaemic stroke † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Loss of consciousness † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Myasthenia gravis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Neurotoxicity † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Seizure † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Syncope † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	2/266 (0.75%)	2	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Transient ischaemic attack † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Vasogenic cerebral oedema † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Psychiatric disorders
Adjustment disorder with depressed mood † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Anxiety † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Confusional state † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Mental status changes † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Suicide attempt † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	2/266 (0.75%)	2	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
Azotaemia † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Nephrolithiasis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Renal artery thrombosis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Renal failure † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Renal impairment † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Urinary retention † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Acute respiratory failure † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Aspiration † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Bronchospasm † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Choking † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/266 (0.75%)	3	3/265 (1.13%)	3	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Chylothorax † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Dyspnoea † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	3/266 (1.13%)	3	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Dyspnoea exertional † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Haemoptysis † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	1/266 (0.38%)	1	1/65 (1.54%)	1	1/61 (1.64%)	1	0/62 (0.00%)	0
Interstitial lung disease † 1	2/266 (0.75%)	2	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Lung disorder † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pleural effusion † 1	1/266 (0.38%)	1	2/265 (0.75%)	2	2/266 (0.75%)	2	0/65 (0.00%)	0	1/61 (1.64%)	1	0/62 (0.00%)	0
Pneumonia aspiration † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pneumonitis † 1	5/266 (1.88%)	5	3/265 (1.13%)	3	3/266 (1.13%)	3	2/65 (3.08%)	2	0/61 (0.00%)	0	0/62 (0.00%)	0
Pneumothorax † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pneumothorax spontaneous † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pulmonary artery thrombosis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pulmonary embolism † 1	7/266 (2.63%)	7	1/265 (0.38%)	1	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Pulmonary haemorrhage † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Pulmonary oedema † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Respiratory failure † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	1/266 (0.38%)	2	1/65 (1.54%)	1	1/61 (1.64%)	1	0/62 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	0/61 (0.00%)	0	0/62 (0.00%)	0
Dermatomyositis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Rash † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Stevens-Johnson syndrome † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Urticaria † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Vascular disorders
Aortic aneurysm † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Arterial stenosis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Deep vein thrombosis † 1	0/266 (0.00%)	0	2/265 (0.75%)	2	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Embolism arterial † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Haemorrhage † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypertension † 1	2/266 (0.75%)	2	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Hypotension † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Peripheral artery thrombosis † 1	0/266 (0.00%)	0	1/265 (0.38%)	1	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Phlebitis † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Superior vena cava occlusion † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Superior vena cava syndrome † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	1/266 (0.38%)	1	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Vena cava thrombosis † 1	1/266 (0.38%)	1	0/265 (0.00%)	0	0/266 (0.00%)	0	0/65 (0.00%)	0	0/61 (0.00%)	0	1/62 (1.61%)	1
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Global Cohort: D + T + EP		Global Cohort: D + EP		Global Cohort: EP		China Cohort: D + T + EP		China Cohort: D + EP		China Cohort: EP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	249/266 (93.61%)		247/265 (93.21%)		248/266 (93.23%)		65/65 (100.00%)		61/61 (100.00%)		61/62 (98.39%)
Blood and lymphatic system disorders
Anaemia † 1	94/266 (35.34%)	115	97/265 (36.60%)	110	116/266 (43.61%)	150	47/65 (72.31%)	79	44/61 (72.13%)	58	44/62 (70.97%)	62
Bone marrow failure † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	5/65 (7.69%)	6	4/61 (6.56%)	9	4/62 (6.45%)	12
Leukocytosis † 1	3/266 (1.13%)	5	4/265 (1.51%)	4	6/266 (2.26%)	6	5/65 (7.69%)	5	2/61 (3.28%)	2	4/62 (6.45%)	4
Leukopenia † 1	33/266 (12.41%)	69	40/265 (15.09%)	87	32/266 (12.03%)	69	28/65 (43.08%)	73	31/61 (50.82%)	65	22/62 (35.48%)	69
Lymphopenia † 1	8/266 (3.01%)	12	5/265 (1.89%)	10	8/266 (3.01%)	13	6/65 (9.23%)	11	1/61 (1.64%)	1	2/62 (3.23%)	3
Neutropenia † 1	112/266 (42.11%)	213	110/265 (41.51%)	221	119/266 (44.74%)	234	26/65 (40.00%)	50	22/61 (36.07%)	40	19/62 (30.65%)	55
Thrombocytopenia † 1	50/266 (18.80%)	68	41/265 (15.47%)	63	48/266 (18.05%)	83	15/65 (23.08%)	28	13/61 (21.31%)	25	14/62 (22.58%)	23
Endocrine disorders
Hyperthyroidism † 1	26/266 (9.77%)	26	26/265 (9.81%)	28	1/266 (0.38%)	1	11/65 (16.92%)	11	7/61 (11.48%)	8	1/62 (1.61%)	1
Hypothyroidism † 1	28/266 (10.53%)	33	25/265 (9.43%)	26	4/266 (1.50%)	4	13/65 (20.00%)	14	7/61 (11.48%)	7	1/62 (1.61%)	1
Gastrointestinal disorders
Diarrhoea † 1	40/266 (15.04%)	54	27/265 (10.19%)	37	29/266 (10.90%)	34	16/65 (24.62%)	26	5/61 (8.20%)	5	5/62 (8.06%)	5
Abdominal pain upper † 1	18/266 (6.77%)	21	14/265 (5.28%)	16	7/266 (2.63%)	8	4/65 (6.15%)	4	7/61 (11.48%)	9	0/62 (0.00%)	0
Constipation † 1	54/266 (20.30%)	65	43/265 (16.23%)	53	52/266 (19.55%)	71	25/65 (38.46%)	39	24/61 (39.34%)	29	22/62 (35.48%)	29
Mouth ulceration † 1	1/266 (0.38%)	1	1/265 (0.38%)	1	4/266 (1.50%)	4	4/65 (6.15%)	6	2/61 (3.28%)	2	1/62 (1.61%)	1
Nausea † 1	85/266 (31.95%)	126	89/265 (33.58%)	147	88/266 (33.08%)	140	31/65 (47.69%)	72	20/61 (32.79%)	51	27/62 (43.55%)	59
Stomatitis † 1	21/266 (7.89%)	23	8/265 (3.02%)	10	8/266 (3.01%)	9	2/65 (3.08%)	2	0/61 (0.00%)	0	1/62 (1.61%)	1
Vomiting † 1	36/266 (13.53%)	44	39/265 (14.72%)	65	42/266 (15.79%)	56	30/65 (46.15%)	62	19/61 (31.15%)	35	23/62 (37.10%)	57
General disorders
Asthenia † 1	37/266 (13.91%)	47	42/265 (15.85%)	50	39/266 (14.66%)	50	10/65 (15.38%)	11	6/61 (9.84%)	8	7/62 (11.29%)	7
Fatigue † 1	53/266 (19.92%)	61	48/265 (18.11%)	61	46/266 (17.29%)	55	6/65 (9.23%)	7	7/61 (11.48%)	7	6/62 (9.68%)	8
Malaise † 1	11/266 (4.14%)	11	7/265 (2.64%)	8	3/266 (1.13%)	3	7/65 (10.77%)	7	6/61 (9.84%)	7	4/62 (6.45%)	6
Non-cardiac chest pain † 1	10/266 (3.76%)	14	14/265 (5.28%)	17	7/266 (2.63%)	8	2/65 (3.08%)	3	1/61 (1.64%)	1	0/62 (0.00%)	0
Oedema peripheral † 1	12/266 (4.51%)	15	16/265 (6.04%)	19	9/266 (3.38%)	10	3/65 (4.62%)	7	1/61 (1.64%)	1	0/62 (0.00%)	0
Pyrexia † 1	36/266 (13.53%)	53	22/265 (8.30%)	24	16/266 (6.02%)	18	23/65 (35.38%)	33	6/61 (9.84%)	9	5/62 (8.06%)	8
Hepatobiliary disorders
Hepatic function abnormal † 1	6/266 (2.26%)	7	1/265 (0.38%)	1	0/266 (0.00%)	0	10/65 (15.38%)	12	4/61 (6.56%)	8	2/62 (3.23%)	3
Infections and infestations
Nasopharyngitis † 1	6/266 (2.26%)	8	10/265 (3.77%)	13	7/266 (2.63%)	8	7/65 (10.77%)	8	2/61 (3.28%)	2	3/62 (4.84%)	3
Pneumonia † 1	13/266 (4.89%)	13	8/265 (3.02%)	10	13/266 (4.89%)	13	5/65 (7.69%)	7	3/61 (4.92%)	4	5/62 (8.06%)	5
Upper respiratory tract infection † 1	17/266 (6.39%)	18	5/265 (1.89%)	6	7/266 (2.63%)	7	12/65 (18.46%)	19	2/61 (3.28%)	3	3/62 (4.84%)	3
Urinary tract infection † 1	8/266 (3.01%)	10	12/265 (4.53%)	16	11/266 (4.14%)	13	4/65 (6.15%)	5	4/61 (6.56%)	7	3/62 (4.84%)	4
Investigations
Alanine aminotransferase increased † 1	20/266 (7.52%)	25	16/265 (6.04%)	21	12/266 (4.51%)	15	17/65 (26.15%)	24	6/61 (9.84%)	6	6/62 (9.68%)	10
Amylase increased † 1	6/266 (2.26%)	7	11/265 (4.15%)	12	2/266 (0.75%)	2	4/65 (6.15%)	5	4/61 (6.56%)	8	0/62 (0.00%)	0
Aspartate aminotransferase increased † 1	19/266 (7.14%)	22	16/265 (6.04%)	21	9/266 (3.38%)	11	11/65 (16.92%)	12	11/61 (18.03%)	13	5/62 (8.06%)	7
Blood alkaline phosphatase increased † 1	11/266 (4.14%)	12	13/265 (4.91%)	17	6/266 (2.26%)	7	2/65 (3.08%)	3	2/61 (3.28%)	2	4/62 (6.45%)	4
Blood bilirubin increased † 1	5/266 (1.88%)	5	3/265 (1.13%)	5	4/266 (1.50%)	5	7/65 (10.77%)	12	3/61 (4.92%)	4	3/62 (4.84%)	6
Blood creatinine increased † 1	3/266 (1.13%)	3	5/265 (1.89%)	5	6/266 (2.26%)	6	6/65 (9.23%)	9	5/61 (8.20%)	9	5/62 (8.06%)	8
Blood lactate dehydrogenase increased † 1	4/266 (1.50%)	5	6/265 (2.26%)	6	8/266 (3.01%)	8	2/65 (3.08%)	3	1/61 (1.64%)	3	5/62 (8.06%)	10
Blood urea increased † 1	0/266 (0.00%)	0	3/265 (1.13%)	3	0/266 (0.00%)	0	2/65 (3.08%)	3	2/61 (3.28%)	2	4/62 (6.45%)	8
Blood urine present † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	1/65 (1.54%)	1	3/61 (4.92%)	3	5/62 (8.06%)	5
Gamma-glutamyltransferase increased † 1	9/266 (3.38%)	10	13/265 (4.91%)	13	6/266 (2.26%)	7	4/65 (6.15%)	6	2/61 (3.28%)	3	3/62 (4.84%)	3
Haemoglobin decreased † 1	0/266 (0.00%)	0	0/265 (0.00%)	0	0/266 (0.00%)	0	2/65 (3.08%)	3	2/61 (3.28%)	2	4/62 (6.45%)	4
Lymphocyte count decreased † 1	2/266 (0.75%)	2	3/265 (1.13%)	3	2/266 (0.75%)	2	4/65 (6.15%)	4	4/61 (6.56%)	7	3/62 (4.84%)	8
Neutrophil count decreased † 1	11/266 (4.14%)	16	26/265 (9.81%)	42	31/266 (11.65%)	49	22/65 (33.85%)	52	28/61 (45.90%)	44	21/62 (33.87%)	71
Platelet count decreased † 1	6/266 (2.26%)	8	16/265 (6.04%)	20	14/266 (5.26%)	22	10/65 (15.38%)	15	10/61 (16.39%)	11	11/62 (17.74%)	17
Weight decreased † 1	19/266 (7.14%)	20	10/265 (3.77%)	10	9/266 (3.38%)	10	7/65 (10.77%)	8	10/61 (16.39%)	12	5/62 (8.06%)	6
White blood cell count decreased † 1	9/266 (3.38%)	11	14/265 (5.28%)	21	17/266 (6.39%)	22	16/65 (24.62%)	34	17/61 (27.87%)	27	24/62 (38.71%)	54
Metabolism and nutrition disorders
Decreased appetite † 1	57/266 (21.43%)	64	48/265 (18.11%)	60	46/266 (17.29%)	54	27/65 (41.54%)	40	27/61 (44.26%)	46	27/62 (43.55%)	54
Hyperglycaemia † 1	5/266 (1.88%)	9	10/265 (3.77%)	14	9/266 (3.38%)	11	1/65 (1.54%)	1	4/61 (6.56%)	5	3/62 (4.84%)	5
Hyperkalaemia † 1	5/266 (1.88%)	10	5/265 (1.89%)	10	7/266 (2.63%)	9	2/65 (3.08%)	5	4/61 (6.56%)	5	0/62 (0.00%)	0
Hyperuricaemia † 1	2/266 (0.75%)	3	4/265 (1.51%)	4	1/266 (0.38%)	1	4/65 (6.15%)	6	3/61 (4.92%)	10	6/62 (9.68%)	14
Hypoalbuminaemia † 1	9/266 (3.38%)	14	5/265 (1.89%)	6	5/266 (1.88%)	8	7/65 (10.77%)	7	3/61 (4.92%)	4	4/62 (6.45%)	6
Hypocalcaemia † 1	4/266 (1.50%)	4	5/265 (1.89%)	6	7/266 (2.63%)	7	2/65 (3.08%)	2	2/61 (3.28%)	2	4/62 (6.45%)	6
Hypochloraemia † 1	5/266 (1.88%)	6	0/265 (0.00%)	0	0/266 (0.00%)	0	5/65 (7.69%)	9	5/61 (8.20%)	6	3/62 (4.84%)	6
Hypokalaemia † 1	19/266 (7.14%)	22	17/265 (6.42%)	21	11/266 (4.14%)	13	9/65 (13.85%)	18	9/61 (14.75%)	12	12/62 (19.35%)	18
Hypomagnesaemia † 1	15/266 (5.64%)	18	18/265 (6.79%)	20	13/266 (4.89%)	14	4/65 (6.15%)	5	1/61 (1.64%)	1	2/62 (3.23%)	4
Hyponatraemia † 1	20/266 (7.52%)	28	26/265 (9.81%)	34	9/266 (3.38%)	11	18/65 (27.69%)	28	10/61 (16.39%)	13	16/62 (25.81%)	20
Hypoproteinaemia † 1	1/266 (0.38%)	2	0/265 (0.00%)	0	1/266 (0.38%)	1	3/65 (4.62%)	5	5/61 (8.20%)	6	5/62 (8.06%)	9
Musculoskeletal and connective tissue disorders
Back pain † 1	30/266 (11.28%)	33	24/265 (9.06%)	32	18/266 (6.77%)	24	3/65 (4.62%)	4	3/61 (4.92%)	4	5/62 (8.06%)	6
Musculoskeletal pain † 1	14/266 (5.26%)	15	10/265 (3.77%)	11	5/266 (1.88%)	6	1/65 (1.54%)	1	4/61 (6.56%)	4	0/62 (0.00%)	0
Pain in extremity † 1	6/266 (2.26%)	6	12/265 (4.53%)	16	4/266 (1.50%)	4	2/65 (3.08%)	2	4/61 (6.56%)	4	0/62 (0.00%)	0
Nervous system disorders
Dizziness † 1	15/266 (5.64%)	20	23/265 (8.68%)	27	12/266 (4.51%)	13	6/65 (9.23%)	7	6/61 (9.84%)	8	5/62 (8.06%)	7
Headache † 1	29/266 (10.90%)	31	17/265 (6.42%)	19	22/266 (8.27%)	25	4/65 (6.15%)	4	4/61 (6.56%)	6	2/62 (3.23%)	3
Paraesthesia † 1	17/266 (6.39%)	17	18/265 (6.79%)	19	13/266 (4.89%)	15	0/65 (0.00%)	0	0/61 (0.00%)	0	0/62 (0.00%)	0
Psychiatric disorders
Insomnia † 1	25/266 (9.40%)	27	23/265 (8.68%)	28	13/266 (4.89%)	14	6/65 (9.23%)	8	6/61 (9.84%)	8	8/62 (12.90%)	13
Renal and urinary disorders
Proteinuria † 1	3/266 (1.13%)	8	1/265 (0.38%)	3	3/266 (1.13%)	5	14/65 (21.54%)	22	9/61 (14.75%)	14	10/62 (16.13%)	14
Respiratory, thoracic and mediastinal disorders
Cough † 1	28/266 (10.53%)	32	35/265 (13.21%)	36	19/266 (7.14%)	20	11/65 (16.92%)	13	8/61 (13.11%)	8	5/62 (8.06%)	5
Dyspnoea † 1	24/266 (9.02%)	31	32/265 (12.08%)	36	27/266 (10.15%)	30	3/65 (4.62%)	5	4/61 (6.56%)	4	4/62 (6.45%)	5
Haemoptysis † 1	18/266 (6.77%)	21	12/265 (4.53%)	13	5/266 (1.88%)	6	2/65 (3.08%)	2	7/61 (11.48%)	7	2/62 (3.23%)	2
Hiccups † 1	10/266 (3.76%)	18	10/265 (3.77%)	16	9/266 (3.38%)	20	5/65 (7.69%)	6	4/61 (6.56%)	4	1/62 (1.61%)	1
Oropharyngeal pain † 1	4/266 (1.50%)	5	10/265 (3.77%)	11	6/266 (2.26%)	7	4/65 (6.15%)	4	0/61 (0.00%)	0	2/62 (3.23%)	2
Productive cough † 1	8/266 (3.01%)	8	10/265 (3.77%)	11	7/266 (2.63%)	8	9/65 (13.85%)	11	6/61 (9.84%)	7	3/62 (4.84%)	3
Skin and subcutaneous tissue disorders
Alopecia † 1	79/266 (29.70%)	80	84/265 (31.70%)	84	92/266 (34.59%)	94	28/65 (43.08%)	29	29/61 (47.54%)	29	27/62 (43.55%)	27
Pruritus † 1	40/266 (15.04%)	52	21/265 (7.92%)	33	10/266 (3.76%)	10	4/65 (6.15%)	14	2/61 (3.28%)	3	1/62 (1.61%)	1
Rash † 1	37/266 (13.91%)	52	16/265 (6.04%)	20	10/266 (3.76%)	10	25/65 (38.46%)	37	12/61 (19.67%)	16	2/62 (3.23%)	2
Vascular disorders
Hypertension † 1	13/266 (4.89%)	15	16/265 (6.04%)	25	7/266 (2.63%)	8	6/65 (9.23%)	13	7/61 (11.48%)	12	3/62 (4.84%)	8
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

Analysis of the China cohort was performed to evaluate the consistency of efficacy and safety in Chinese patients with the global cohort in order to meet regulatory requirements and was not powered for a formal assessment of statistical significance.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Global Clinical Lead
• Organization: AstraZeneca
• Phone: 1-877-240-9479
• EMail: information.center@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03043872
• Other Study ID Numbers: D419QC00001; 2016-001203-23 ( EudraCT Number )
• First Submitted: January 18, 2017
• First Posted: February 6, 2017
• Results First Submitted: January 21, 2021
• Results First Posted: March 4, 2021
• Last Update Posted: December 21, 2023