Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON). (POSEIDON)

• ClinicalTrials.gov Identifier: NCT03164616
• Recruitment Status: Active, not recruiting
• First Posted: May 23, 2017
• Results First Posted: April 7, 2022
• Last Update Posted: March 5, 2024
• 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: Non Small Cell Lung Cancer NSCLC
• Interventions: Drug: Durvalumab; Drug: Tremelimumab; Drug: Abraxane + carboplatin; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + carboplatin; Drug: Pemetrexed + carboplatin; Drug: Pemetrexed + cisplatin
• Enrollment: 1186

Participant Flow

Recruitment Details

Study was conducted in 142 study centers across 18 countries in North and Latin America, Europe, Asia Pacific and Africa. First patient randomized: 27 June 2017. Results are presented for the global cohort at final analysis data cut-offs (DCOs) of 24 July 2019 (Response Evaluation Criteria in Solid Tumors [RECIST]-based endpoints) and 12 March 2021 (all other data). Once global enrollment was complete, enrollment was started in mainland China. Results for the China cohort will be reported later.

Pre-assignment Details

Patients were randomized in a stratified manner as per programmed cell death ligand 1 (PD-L1) tumor expression status (PD-L1 tumor cells [TC] ≥50% versus [vs] <50%), disease stage (IVA vs IVB), and histology (non-squamous vs squamous) in a 1:1:1 ratio to receive treatment with tremelimumab + durvalumab combination therapy + standard of care (SoC) chemotherapy (also referred to as T+ D + SoC), durvalumab monotherapy + SoC chemotherapy (also referred to as D + SoC), or SoC chemotherapy alone.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description	During chemotherapy (combination) stage: Patients received tremelimumab 75 milligrams (mg) + durvalumab 1500 mg combination therapy + SoC chemotherapy via intravenous (IV) infusion every 3 weeks (Q3W) for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Period Title: Overall Study
Started [1]	338	338	337
Received Treatment	331	335	331
Completed [2]	80	65	40
Not Completed	258	273	297
Reason Not Completed
Death	250	264	279
Lost to Follow-up	2	2	2
Withdrawal by Subject	6	7	16
[1] Randomized and included in global cohort analysis; [2] Completed study or ongoing in study at primary completion date (global cohort final analysis DCO of 12 March 2021)

Baseline Characteristics

Arm/Group Title		T + D + SoC	D + SoC	SoC Alone	Total
Arm/Group Description		During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.	Total of all reporting groups
Overall Number of Baseline Participants		338	338	337	1013
Baseline Analysis Population Description		Global cohort: All patients in the full analysis set (FAS), which included all randomized patients, were included in the baseline analysis. Patients were included in the analysis in the treatment arm to which they were randomized, regardless of the treatment they received.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	338 participants	338 participants	337 participants	1013 participants
		62.6 (9.43)	63.5 (9.10)	63.1 (9.87)	63.1 (9.47)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	338 participants	338 participants	337 participants	1013 participants
	Female	69 20.4%	85 25.1%	89 26.4%	243 24.0%
	Male	269 79.6%	253 74.9%	248 73.6%	770 76.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	338 participants	338 participants	337 participants	1013 participants
	White	205 60.7%	182 53.8%	179 53.1%	566 55.9%
	Black or African American	8 2.4%	4 1.2%	8 2.4%	20 2.0%
	Asian	99 29.3%	123 36.4%	128 38.0%	350 34.6%
	Native Hawaiian or other Pacific Islander	2 0.6%	0 0.0%	0 0.0%	2 0.2%
	American Indian or Alaska Native	12 3.6%	17 5.0%	9 2.7%	38 3.8%
	Other	12 3.6%	12 3.6%	13 3.9%	37 3.7%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	338 participants	338 participants	337 participants	1013 participants
	Hispanic or Latino	51 15.1%	54 16.0%	55 16.3%	160 15.8%
	Not Hispanic or Latino	287 84.9%	284 84.0%	282 83.7%	853 84.2%
Age Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	338 participants	338 participants	337 participants	1013 participants
	≥18 to <50	29 8.6%	27 8.0%	30 8.9%	86 8.5%
	≥50 to <65	162 47.9%	142 42.0%	146 43.3%	450 44.4%
	≥65 to <75	112 33.1%	130 38.5%	121 35.9%	363 35.8%
	≥75	35 10.4%	39 11.5%	40 11.9%	114 11.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
Description	PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] 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. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity).
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. Analysis of PFS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure.

Arm/Group Title	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	338	337
Median (95% Confidence Interval); Unit of Measure: months
	5.5; (4.7 to 6.5)	4.8; (4.6 to 5.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D + SoC, SoC Alone
	Comments	D + SoC vs SoC alone. A hazard ratio (HR) <1 favors D + SoC to be associated with a longer PFS than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00093
	Comments	Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.620 to 0.885
	Estimation Comments	The HR and confidence interval (CI) were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

2. Primary Outcome

Title	Overall Survival (OS); D + SoC Compared With SoC Alone
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. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity).
Time Frame	From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. Analysis of OS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure.

Arm/Group Title	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	338	337
Median (95% Confidence Interval); Unit of Measure: months
	13.3; (11.4 to 14.7)	11.7; (10.5 to 13.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D + SoC, SoC Alone
	Comments	D + SoC vs SoC alone. An HR <1 favors D + SoC to be associated with a longer OS than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.07581
	Comments	Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.724 to 1.016
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

3. Secondary Outcome

Title	PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
Description	PFS (per RECIST 1.1 using BICR 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. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months.

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	338	338	337
Median (95% Confidence Interval); Unit of Measure: months
	6.2; (5.0 to 6.5)	5.5; (4.7 to 6.5)	4.8; (4.6 to 5.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	T + D + SoC, SoC Alone
	Comments	T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer PFS than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00031
	Comments	Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.600 to 0.860
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

4. Secondary Outcome

Title	OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
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.
Time Frame	From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	338	338	337
Median (95% Confidence Interval); Unit of Measure: months
	14.0; (11.7 to 16.1)	13.3; (11.4 to 14.7)	11.7; (10.5 to 13.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	T + D + SoC, SoC Alone
	Comments	T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer OS than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00304
	Comments	Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.650 to 0.916
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

5. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR (per RECIST 1.1 using BICR assessments) was defined as the percentage of patients with at least one visit response of complete response (CR) or partial response (PR). Results are presented for the pre-specified ORR analysis using unconfirmed responses based on BICR.
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. The denominator was a subset of the FAS who had measurable disease at baseline.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	335	330	332
Measure Type: Number; Unit of Measure: percentage of patients
	46.3	48.5	33.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D + SoC, SoC Alone
	Comments	D + SoC vs SoC alone. An odds ratio >1 favors D + SoC compared to SoC alone. Analysis was performed using logistic regression adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB), with the CI calculated using a profile likelihood approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 1.382 to 2.619
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	T + D + SoC, SoC Alone
	Comments	T + D + SoC vs SoC alone. An odds ratio >1 favors T + D + SoC compared to SoC alone. Analysis was performed using logistic regression adjusting for PD-L1 tumor expression (TC ≥50% vs TC <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB), with the CI calculated using a profile likelihood approach.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) 95%; 1.260 to 2.367
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Best Objective Response (BoR)
Description	The BoR was calculated based on the overall visit responses from each RECIST 1.1 assessment. BOR was defined as the best response a patient had following randomization, but prior to starting any subsequent cancer therapy and up to and including RECIST 1.1 progression or the last evaluable assessment in the absence of RECIST 1.1 progression, as determined by BICR. Categorization of BoR was based on RECIST using the following 'response' categories: CR and PR and the following 'non-response' categories: stable disease (SD) ≥6 weeks, progression (ie, PD) and not evaluable (NE). Results are presented for number (%) of patients in each specified category.
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. The denominator was a subset of the FAS who had measurable disease at baseline.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	335	330	332
Measure Type: Count of Participants; Unit of Measure: Participants
CR	2 0.6%	3 0.9%	0 0.0%
PR	153 45.7%	157 47.6%	111 33.4%
SD ≥6 weeks	120 35.8%	107 32.4%	150 45.2%
PD	48 14.3%	60 18.2%	61 18.4%
NE	12 3.6%	3 0.9%	10 3.0%

7. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR (per RECIST 1.1 using BICR assessments) was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response coincided with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of the initial response was defined as the latest of the dates contributing towards the first visit of PR or CR. Results are presented for the pre-specified DoR analysis using unconfirmed responses based on BICR.
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. Only patients with an objective response were included in the analysis.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	155	160	111
Median (Inter-Quartile Range); Unit of Measure: months
	7.4 [1]; (3.5 to NA)	6.0 [1]; (3.4 to NA)	4.2; (3.0 to 6.9)

[1]

75th percentile could not be calculated as it was not reached.

8. Secondary Outcome

Title	Time From Randomization to Second Progression (PFS2)
Description	PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS) or death. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of: objective radiological imaging, symptomatic progression or death.
Time Frame	Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients.

Arm/Group Title	T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	338	338	337
Median (95% Confidence Interval); Unit of Measure: months
	10.4; (9.4 to 12.2)	10.2; (9.0 to 11.5)	9.4; (8.6 to 10.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D + SoC, SoC Alone
	Comments	D + SoC vs SoC alone. An HR <1 favors D + SoC to be associated with a longer PFS2 than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.666 to 0.928
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	T + D + SoC, SoC Alone
	Comments	T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer PFS2 than SoC alone.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.632 to 0.883
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.

9. Secondary Outcome

Title	Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
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), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.

Outcome Measure Data

Analysis Population Description

Global cohort: The PK analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol for whom any post-dose PK data were available and without any protocol deviations that would significantly affect the PK analyses. PK for durvalumab was performed for the T + D + SoC and D + SoC treatment arms only.

Arm/Group Title		T + D + SoC	D + SoC
Arm/Group Description:		During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed		327	330
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms/milliliter (μg/mL)
Week 0	Number Analyzed	286 participants	303 participants
		418.80; (164.20%)	505.01; (48.76%)
Week 3	Number Analyzed	284 participants	285 participants
		82.08; (84.38%)	91.53; (100.58%)
Week 12	Number Analyzed	218 participants	226 participants
		195.62; (58.65%)	212.11; (60.37%)
Follow-up (3 months)	Number Analyzed	59 participants	53 participants
		13.42; (166.36%)	16.06; (249.88%)

10. Secondary Outcome

Title	PK of Tremelimumab; Peak and Trough Serum Concentrations
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), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.

Outcome Measure Data

Analysis Population Description

Global cohort: The PK analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol for whom any post-dose PK data were available and without any protocol deviations that would significantly affect the PK analyses. PK for tremelimumab was performed for the T + D + SoC treatment arm only.

Arm/Group Title		T + D + SoC
Arm/Group Description:		During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed		327
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: μg/mL
Week 0	Number Analyzed	294 participants
		23.17; (65.62%)
Week 3	Number Analyzed	285 participants
		4.16; (80.83%)
Week 12	Number Analyzed	183 participants
		7.82; (75.68%)
Follow-up (3 months)	Number Analyzed	105 participants
		0.86; (87.65%)

11. Secondary Outcome

Title	Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
Description	Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against durvalumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is 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.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).

Outcome Measure Data

Analysis Population Description

Global cohort: The ADA evaluable patients included those in the safety analysis set with non-missing baseline ADA sample and at least 1 post-baseline ADA sample. ADA for durvalumab was performed for the T + D + SoC and D + SoC treatment arms only. The denominator was durvalumab ADA evaluable patients.

Arm/Group Title	T + D + SoC	D + SoC
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	286	285
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	42 14.7%	33 11.6%
Treatment-emergent ADA positive (ADA incidence)	29 10.1%	19 6.7%
Treatment-boosted ADA	2 0.7%	1 0.4%
Treatment-induced ADA (ADA positive post-baseline only)	27 9.4%	18 6.3%
ADA positive at baseline only	8 2.8%	13 4.6%
ADA positive post-baseline and positive at baseline	7 2.4%	2 0.7%
Persistently positive	8 2.8%	7 2.5%
Transiently positive	26 9.1%	13 4.6%
nAb positive at any visit	3 1.0%	3 1.1%

12. Secondary Outcome

Title	Number of Patients With ADA Response to Tremelimumab
Description	Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against tremelimumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is 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.
Time Frame	Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).

Outcome Measure Data

Analysis Population Description

Global cohort: The ADA evaluable patients included those in the safety analysis set with non-missing baseline ADA sample and at least 1 post-baseline ADA sample. ADA for tremelimumab was performed for the T + D + SoC treatment arm only. The denominator was tremelimumab ADA evaluable patients.

Arm/Group Title	T + D + SoC
Arm/Group Description:	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed	278
Measure Type: Count of Participants; Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)	44 15.8%
Treatment-emergent ADA positive (ADA incidence)	38 13.7%
Treatment-boosted ADA	3 1.1%
Treatment-induced ADA (ADA positive post-baseline only)	35 12.6%
ADA positive at baseline only	4 1.4%
ADA positive post-baseline and positive at baseline	5 1.8%
Persistently positive	22 7.9%
Transiently positive	18 6.5%
nAb positive at any visit	31 11.2%

13. Secondary Outcome

Title	Time to Deterioration of Global Health Status / 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)
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 was defined as time from randomization until the date of first clinically meaningful deterioration that was 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 came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. 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		T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:		During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed		325	326	321
Median (95% Confidence Interval); Unit of Measure: months
QLQ-C30 Global Health Status / HRQoL	Number Analyzed	319 participants	321 participants	318 participants
		8.3; (6.4 to 10.2)	7.8; (6.5 to 9.5)	5.6; (4.4 to 7.5)
QLQ-C30 Physical Functioning	Number Analyzed	323 participants	325 participants	320 participants
		7.7; (5.9 to 9.4)	8.3; (6.6 to 10.0)	5.3; (4.2 to 6.5)
QLQ-C30 Role Functioning	Number Analyzed	314 participants	313 participants	304 participants
		6.6; (5.4 to 8.3)	7.4; (5.8 to 9.3)	4.8; (3.6 to 6.2)
QLQ-C30 Cognitive Functioning	Number Analyzed	323 participants	323 participants	318 participants
		7.6; (6.1 to 9.7)	7.4; (5.6 to 9.3)	5.8; (4.6 to 7.5)
QLQ-C30 Emotional Functioning	Number Analyzed	322 participants	322 participants	315 participants
		8.5; (6.6 to 11.3)	9.5; (7.4 to 12.0)	7.5; (5.8 to 11.0)
QLQ-C30 Social Functioning	Number Analyzed	320 participants	319 participants	314 participants
		6.4; (5.6 to 9.4)	7.1; (5.0 to 9.6)	5.7; (4.6 to 7.4)
QLQ-C30 Fatigue	Number Analyzed	317 participants	318 participants	314 participants
		3.7; (2.8 to 5.0)	3.8; (2.9 to 4.9)	2.8; (2.1 to 3.7)
QLQ-C30 Pain	Number Analyzed	316 participants	311 participants	298 participants
		8.9; (6.2 to 10.9)	6.5; (5.6 to 8.6)	5.7; (4.6 to 7.2)
QLQ-C30 Nausea / Vomiting	Number Analyzed	322 participants	322 participants	319 participants
		7.8; (5.6 to 10.0)	5.6; (4.1 to 6.6)	5.6; (4.2 to 7.5)
QLQ-C30 Dyspnea	Number Analyzed	310 participants	310 participants	301 participants
		7.9; (5.8 to 9.8)	6.9; (5.8 to 8.9)	6.7; (5.5 to 8.8)
QLQ-C30 Insomnia	Number Analyzed	311 participants	304 participants	301 participants
		8.3; (6.4 to 10.4)	7.4; (5.6 to 9.8)	5.8; (4.2 to 7.2)
QLQ-C30 Appetite Loss	Number Analyzed	308 participants	316 participants	305 participants
		7.2; (5.7 to 9.4)	7.2; (4.7 to 8.8)	7.0; (5.6 to 9.6)
QLQ-C30 Constipation	Number Analyzed	315 participants	314 participants	306 participants
		9.2; (6.4 to 12.2)	8.7; (6.5 to 10.0)	6.1; (4.8 to 7.5)
QLQ-C30 Diarrhea	Number Analyzed	324 participants	324 participants	320 participants
		11.0; (9.3 to 13.6)	9.8; (8.1 to 12.9)	10.8; (9.2 to 15.1)

14. Secondary Outcome

Title	Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
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 treatment-related symptoms 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 was defined as time from randomization until the date of first clinically meaningful deterioration that was 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 came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Outcome Measure Data

Analysis Population Description

Global cohort: The FAS included all randomized patients. For QLQ-LC13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

Arm/Group Title		T + D + SoC	D + SoC	SoC Alone
Arm/Group Description:		During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.	During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
Overall Number of Participants Analyzed		325	326	321
Median (95% Confidence Interval); Unit of Measure: months
QLQ-LC13 Cough	Number Analyzed	302 participants	314 participants	295 participants
		9.7; (7.3 to 13.3)	11.0; (8.7 to 13.5)	8.8; (6.8 to 12.3)
QLQ-LC13 Hemoptysis	Number Analyzed	325 participants	326 participants	318 participants
		17.8; (12.5 to 31.3)	14.0; (10.3 to 21.4)	11.4; (9.3 to 19.3)
QLQ-LC13 Dyspnea	Number Analyzed	325 participants	325 participants	316 participants
		5.4; (4.2 to 6.4)	5.0; (3.8 to 6.4)	3.6; (2.6 to 4.5)
QLQ-LC13 Pain in Chest	Number Analyzed	319 participants	322 participants	309 participants
		10.0; (7.7 to 13.3)	9.5; (7.8 to 11.8)	8.6; (6.8 to 11.4)
QLQ-LC13 Pain in Arm or Shoulder	Number Analyzed	312 participants	311 participants	310 participants
		8.9; (6.6 to 10.9)	8.9; (7.4 to 10.3)	8.8; (6.2 to 12.0)
QLQ-LC13 Pain in Other Parts	Number Analyzed	312 participants	314 participants	306 participants
		9.7; (6.8 to 12.1)	8.9; (6.8 to 11.2)	5.8; (4.9 to 9.3)

Adverse Events

Time Frame	Adverse events: from first dose of study treatment until the earlier of 90 days after last dose or the date of first subsequent anticancer therapy. All-cause mortality (death due to any cause): from randomization up to global cohort final analysis DCO (12 March 2021). Maximum timeframe of approximately 45 months.
Adverse Event Reporting Description	Safety analysis set included all patients who received at least 1 dose of study treatment (analyzed according to actual treatment received). 1 patient randomized to T + D + SoC arm and 1 patient randomized to D + SoC arm only received SoC and were included in SoC alone arm of the safety analysis set. All-cause mortality was determined for patients in the FAS (analyzed according to randomized treatment arm, regardless of the treatment received). Results are reported for the global cohort only.
Arm/Group Title	T + D + SoC		D + SoC		SoC Alone
Arm/Group Description	During chemotherapy (combination) stage: Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 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 (in combination with durvalumab) at Week 16 post-chemotherapy. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.		During chemotherapy (combination) stage: Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.		During chemotherapy (combination) stage: Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up. The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only). Post-chemotherapy (maintenance) stage: Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.
All-Cause Mortality
	T + D + SoC		D + SoC		SoC Alone
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	251/338 (74.26%)		265/338 (78.40%)		285/337 (84.57%)
Serious Adverse Events
	T + D + SoC		D + SoC		SoC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/330 (44.24%)		134/334 (40.12%)		117/333 (35.14%)
Blood and lymphatic system disorders
Leukopenia † 1	2/330 (0.61%)	3	1/334 (0.30%)	1	1/333 (0.30%)	1
Anaemia † 1	18/330 (5.45%)	32	23/334 (6.89%)	30	21/333 (6.31%)	25
Neutropenia † 1	4/330 (1.21%)	5	6/334 (1.80%)	8	3/333 (0.90%)	5
Pancytopenia † 1	2/330 (0.61%)	2	5/334 (1.50%)	6	3/333 (0.90%)	4
Thrombocytopenia † 1	8/330 (2.42%)	8	6/334 (1.80%)	7	3/333 (0.90%)	3
Disseminated intravascular coagulation † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	1/333 (0.30%)	1
Febrile neutropenia † 1	7/330 (2.12%)	7	5/334 (1.50%)	5	4/333 (1.20%)	4
Cardiac disorders
Acute coronary syndrome † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Acute myocardial infarction † 1	2/330 (0.61%)	2	3/334 (0.90%)	3	1/333 (0.30%)	1
Angina pectoris † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Angina unstable † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Atrial fibrillation † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	0/333 (0.00%)	0
Atrial tachycardia † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Autoimmune myocarditis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Bundle branch block left † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cardiac arrest † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cardiac failure † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	3/333 (0.90%)	3
Cardiac failure acute † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cardiac failure congestive † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Cardiac tamponade † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Cardiopulmonary failure † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	1/333 (0.30%)	1
Coronary artery disease † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	0/333 (0.00%)	0
Myocardial infarction † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Pericardial effusion † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Right ventricular failure † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Supraventricular tachycardia † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Tachyarrhythmia † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Ventricular fibrillation † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Ear and labyrinth disorders
Deafness bilateral † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Deafness unilateral † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	3/330 (0.91%)	3	2/334 (0.60%)	2	0/333 (0.00%)	0
Diabetes insipidus † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Hypopituitarism † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	0/333 (0.00%)	0
Eye disorders
Cataract † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	2
Gastrointestinal disorders
Abdominal discomfort † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Abdominal pain upper † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Autoimmune pancreatitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Colitis † 1	5/330 (1.52%)	5	3/334 (0.90%)	3	0/333 (0.00%)	0
Diarrhoea † 1	8/330 (2.42%)	8	3/334 (0.90%)	4	2/333 (0.60%)	2
Diverticular perforation † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Duodenal ulcer haemorrhage † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Dysphagia † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Enteritis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Enterocolitis † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Faecaloma † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Gastric ulcer † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Gastric ulcer haemorrhage † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	1/333 (0.30%)	1
Gastric ulcer perforation † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Gastritis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Gastrointestinal haemorrhage † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Gastrointestinal inflammation † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Inguinal hernia † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Intestinal obstruction † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Mesenteric vein thrombosis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Nausea † 1	2/330 (0.61%)	2	1/334 (0.30%)	2	2/333 (0.60%)	2
Oesophageal obstruction † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Oesophageal stenosis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Oesophagitis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Pancreatitis † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	1/333 (0.30%)	1
Peptic ulcer † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Small intestinal obstruction † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	1/333 (0.30%)	1
Vomiting † 1	2/330 (0.61%)	2	2/334 (0.60%)	2	0/333 (0.00%)	0
General disorders
Asthenia † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	2/333 (0.60%)	2
Cardiac death † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Death † 1	3/330 (0.91%)	3	6/334 (1.80%)	6	1/333 (0.30%)	1
Face oedema † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Fatigue † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
General physical health deterioration † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Malaise † 1	0/330 (0.00%)	0	1/334 (0.30%)	2	0/333 (0.00%)	0
Oedema peripheral † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Pyrexia † 1	8/330 (2.42%)	8	1/334 (0.30%)	1	1/333 (0.30%)	1
Sudden death † 1	1/330 (0.30%)	1	3/334 (0.90%)	3	0/333 (0.00%)	0
Hepatobiliary disorders
Autoimmune hepatitis † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Cholangitis † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Cholecystitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Drug-induced liver injury † 1	3/330 (0.91%)	3	0/334 (0.00%)	0	0/333 (0.00%)	0
Hepatic failure † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Hepatitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Immune-mediated hepatitis † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Drug hypersensitivity † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Haemophagocytic lymphohistiocytosis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Hypersensitivity † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Infections and infestations
Abscess oral † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Acute hepatitis B † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Appendicitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Arthritis bacterial † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Bronchitis † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Bronchitis bacterial † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
COVID-19 † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
COVID-19 pneumonia † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	1/333 (0.30%)	1
Candida pneumonia † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cellulitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	3/333 (0.90%)	4
Chikungunya virus infection † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Cystitis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cytomegalovirus colitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Device related infection † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Diarrhoea infectious † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Disseminated tuberculosis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Empyema † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	1/333 (0.30%)	1
Encephalitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Encephalitis viral † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Enterocolitis infectious † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Gastroenteritis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Gastroenteritis viral † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Herpes zoster † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Infection † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Influenza † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Lower respiratory tract infection † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	2/333 (0.60%)	2
Neutropenic sepsis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	2/333 (0.60%)	3
Nosocomial infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Ophthalmic herpes zoster † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Oral candidiasis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Perirectal abscess † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Pharyngitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Pleural infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Pneumocystis jirovecii pneumonia † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Pneumonia † 1	36/330 (10.91%)	42	21/334 (6.29%)	23	16/333 (4.80%)	17
Pneumonia bacterial † 1	1/330 (0.30%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Pneumonia klebsiella † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Postoperative wound infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Pulmonary sepsis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Pyelonephritis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Respiratory tract infection † 1	3/330 (0.91%)	4	0/334 (0.00%)	0	0/333 (0.00%)	0
Sepsis † 1	5/330 (1.52%)	5	2/334 (0.60%)	2	2/333 (0.60%)	2
Septic shock † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	1/333 (0.30%)	1
Staphylococcal infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Tracheitis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Tracheobronchitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Upper respiratory tract infection † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	2/333 (0.60%)	2
Urinary tract infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	2/333 (0.60%)	2
Vascular device infection † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Viral infection † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Injury, poisoning and procedural complications
Femoral neck fracture † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	0/333 (0.00%)	0
Femur fracture † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Foot fracture † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Hip fracture † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	2/333 (0.60%)	2
Infusion related reaction † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Radiation oesophagitis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Road traffic accident † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Spinal compression fracture † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Subdural haematoma † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Subdural haemorrhage † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Toxicity to various agents † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Upper limb fracture † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Investigations
Alanine aminotransferase increased † 1	2/330 (0.61%)	2	3/334 (0.90%)	3	0/333 (0.00%)	0
Aspartate aminotransferase increased † 1	0/330 (0.00%)	0	3/334 (0.90%)	3	0/333 (0.00%)	0
Lipase increased † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Neutrophil count decreased † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	3/333 (0.90%)	6
Platelet count decreased † 1	2/330 (0.61%)	2	2/334 (0.60%)	2	1/333 (0.30%)	1
Transaminases increased † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
White blood cell count decreased † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	1/333 (0.30%)	1
Metabolism and nutrition disorders
Cachexia † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Decreased appetite † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	1/333 (0.30%)	1
Dehydration † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	2/333 (0.60%)	2
Fluid overload † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Hypercalcaemia † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	1/333 (0.30%)	1
Hyperglycaemia † 1	2/330 (0.61%)	2	3/334 (0.90%)	3	1/333 (0.30%)	1
Hyperkalaemia † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Hypokalaemia † 1	2/330 (0.61%)	2	2/334 (0.60%)	2	0/333 (0.00%)	0
Hyponatraemia † 1	3/330 (0.91%)	4	0/334 (0.00%)	0	1/333 (0.30%)	1
Type 1 diabetes mellitus † 1	1/330 (0.30%)	2	1/334 (0.30%)	1	0/333 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	1/333 (0.30%)	1
Arthritis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Back pain † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Bone pain † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	0/333 (0.00%)	0
Intervertebral disc protrusion † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Mandibular mass † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Muscular weakness † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Musculoskeletal chest pain † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Musculoskeletal pain † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Myositis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Polymyositis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer fatigue † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Cancer pain † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Colon cancer † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	0/333 (0.00%)	0
Eyelid naevus † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Neuroendocrine carcinoma metastatic † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Rectal cancer † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Tumour associated fever † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Nervous system disorders
Brain oedema † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Cerebral infarction † 1	3/330 (0.91%)	3	2/334 (0.60%)	2	3/333 (0.90%)	4
Cerebral ischaemia † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Cerebrovascular accident † 1	4/330 (1.21%)	4	1/334 (0.30%)	1	1/333 (0.30%)	1
Coordination abnormal † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Dizziness † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Encephalitis autoimmune † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Haemorrhagic stroke † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Headache † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	2/333 (0.60%)	2
Hemiplegia † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Ischaemic stroke † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Leukoencephalopathy † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Nervous system disorder † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Polyneuropathy in malignant disease † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Seizure † 1	2/330 (0.61%)	2	1/334 (0.30%)	1	1/333 (0.30%)	1
Spinal cord disorder † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Syncope † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Transient ischaemic attack † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Vocal cord paralysis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	2/333 (0.60%)	2
Product Issues
Device occlusion † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Completed suicide † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Suicide attempt † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	6/330 (1.82%)	6	4/334 (1.20%)	4	1/333 (0.30%)	1
Autoimmune nephritis † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Bladder mass † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Calculus urinary † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Chronic kidney disease † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	2
Glomerulonephritis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Nephritis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Renal failure † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Renal impairment † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Reproductive system and breast disorders
Uterine haemorrhage † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/330 (0.61%)	3	2/334 (0.60%)	2	5/333 (1.50%)	8
Dyspnoea † 1	3/330 (0.91%)	3	1/334 (0.30%)	1	2/333 (0.60%)	2
Epistaxis † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Haemoptysis † 1	2/330 (0.61%)	2	7/334 (2.10%)	8	3/333 (0.90%)	3
Interstitial lung disease † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Lung infiltration † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Pleural effusion † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	2/333 (0.60%)	2
Pneumonia aspiration † 1	0/330 (0.00%)	0	2/334 (0.60%)	2	1/333 (0.30%)	1
Pneumonitis † 1	6/330 (1.82%)	6	5/334 (1.50%)	5	1/333 (0.30%)	1
Pneumothorax † 1	2/330 (0.61%)	2	0/334 (0.00%)	0	0/333 (0.00%)	0
Pulmonary artery thrombosis † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Pulmonary embolism † 1	5/330 (1.52%)	5	4/334 (1.20%)	4	9/333 (2.70%)	9
Pulmonary haemorrhage † 1	0/330 (0.00%)	0	2/334 (0.60%)	3	3/333 (0.90%)	3
Respiratory failure † 1	1/330 (0.30%)	1	1/334 (0.30%)	1	0/333 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug eruption † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Pemphigoid † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Rash † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	0/333 (0.00%)	0
Rash maculo-papular † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Vascular disorders
Brachiocephalic vein thrombosis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Deep vein thrombosis † 1	3/330 (0.91%)	3	0/334 (0.00%)	0	1/333 (0.30%)	1
Embolism † 1	1/330 (0.30%)	1	2/334 (0.60%)	2	1/333 (0.30%)	1
Haematoma † 1	0/330 (0.00%)	0	0/334 (0.00%)	0	1/333 (0.30%)	1
Hypertensive crisis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Hypotension † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Lymphoedema † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Peripheral artery occlusion † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	0/333 (0.00%)	0
Shock † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Shock haemorrhagic † 1	0/330 (0.00%)	0	1/334 (0.30%)	1	1/333 (0.30%)	1
Superior vena cava syndrome † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
Vasculitis † 1	1/330 (0.30%)	1	0/334 (0.00%)	0	0/333 (0.00%)	0
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	T + D + SoC		D + SoC		SoC Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	309/330 (93.64%)		302/334 (90.42%)		301/333 (90.39%)
Blood and lymphatic system disorders
Leukopenia † 1	41/330 (12.42%)	80	32/334 (9.58%)	59	39/333 (11.71%)	80
Anaemia † 1	150/330 (45.45%)	213	137/334 (41.02%)	188	146/333 (43.84%)	203
Neutropenia † 1	98/330 (29.70%)	177	75/334 (22.46%)	135	77/333 (23.12%)	161
Thrombocytopenia † 1	56/330 (16.97%)	83	38/334 (11.38%)	67	54/333 (16.22%)	77
Endocrine disorders
Hyperthyroidism † 1	19/330 (5.76%)	20	20/334 (5.99%)	21	2/333 (0.60%)	3
Hypothyroidism † 1	39/330 (11.82%)	42	21/334 (6.29%)	24	4/333 (1.20%)	4
Gastrointestinal disorders
Abdominal pain † 1	19/330 (5.76%)	22	16/334 (4.79%)	19	10/333 (3.00%)	10
Constipation † 1	63/330 (19.09%)	85	72/334 (21.56%)	98	79/333 (23.72%)	96
Diarrhoea † 1	65/330 (19.70%)	98	57/334 (17.07%)	72	49/333 (14.71%)	66
Nausea † 1	136/330 (41.21%)	281	120/334 (35.93%)	258	121/333 (36.34%)	243
Stomatitis † 1	17/330 (5.15%)	18	20/334 (5.99%)	25	16/333 (4.80%)	17
Vomiting † 1	59/330 (17.88%)	82	51/334 (15.27%)	74	45/333 (13.51%)	80
General disorders
Asthenia † 1	56/330 (16.97%)	67	31/334 (9.28%)	42	39/333 (11.71%)	49
Fatigue † 1	81/330 (24.55%)	116	80/334 (23.95%)	119	74/333 (22.22%)	93
Mucosal inflammation † 1	17/330 (5.15%)	19	11/334 (3.29%)	15	6/333 (1.80%)	6
Oedema peripheral † 1	27/330 (8.18%)	35	23/334 (6.89%)	29	30/333 (9.01%)	34
Pyrexia † 1	48/330 (14.55%)	65	30/334 (8.98%)	38	22/333 (6.61%)	30
Infections and infestations
Upper respiratory tract infection † 1	22/330 (6.67%)	32	12/334 (3.59%)	13	18/333 (5.41%)	27
Investigations
Alanine aminotransferase increased † 1	45/330 (13.64%)	66	43/334 (12.87%)	63	44/333 (13.21%)	59
Amylase increased † 1	28/330 (8.48%)	47	24/334 (7.19%)	41	16/333 (4.80%)	27
Aspartate aminotransferase increased † 1	42/330 (12.73%)	67	36/334 (10.78%)	59	38/333 (11.41%)	51
Blood creatinine increased † 1	21/330 (6.36%)	33	12/334 (3.59%)	16	12/333 (3.60%)	21
Gamma-glutamyltransferase increased † 1	18/330 (5.45%)	18	17/334 (5.09%)	20	11/333 (3.30%)	11
Lipase increased † 1	20/330 (6.06%)	34	12/334 (3.59%)	23	7/333 (2.10%)	12
Neutrophil count decreased † 1	39/330 (11.82%)	66	46/334 (13.77%)	96	59/333 (17.72%)	110
Platelet count decreased † 1	22/330 (6.67%)	28	19/334 (5.69%)	24	29/333 (8.71%)	35
Weight decreased † 1	23/330 (6.97%)	23	29/334 (8.68%)	30	20/333 (6.01%)	24
White blood cell count decreased † 1	24/330 (7.27%)	44	21/334 (6.29%)	50	27/333 (8.11%)	53
Metabolism and nutrition disorders
Decreased appetite † 1	92/330 (27.88%)	115	71/334 (21.26%)	89	81/333 (24.32%)	117
Hyperglycaemia † 1	18/330 (5.45%)	28	18/334 (5.39%)	25	12/333 (3.60%)	13
Hypokalaemia † 1	25/330 (7.58%)	38	11/334 (3.29%)	19	14/333 (4.20%)	20
Hyponatraemia † 1	9/330 (2.73%)	12	16/334 (4.79%)	19	18/333 (5.41%)	25
Musculoskeletal and connective tissue disorders
Arthralgia † 1	41/330 (12.42%)	55	28/334 (8.38%)	31	20/333 (6.01%)	23
Back pain † 1	25/330 (7.58%)	27	16/334 (4.79%)	21	15/333 (4.50%)	16
Musculoskeletal chest pain † 1	18/330 (5.45%)	21	9/334 (2.69%)	9	20/333 (6.01%)	20
Pain in extremity † 1	17/330 (5.15%)	20	8/334 (2.40%)	9	8/333 (2.40%)	8
Nervous system disorders
Dizziness † 1	20/330 (6.06%)	22	22/334 (6.59%)	28	9/333 (2.70%)	15
Headache † 1	37/330 (11.21%)	49	23/334 (6.89%)	29	24/333 (7.21%)	26
Psychiatric disorders
Insomnia † 1	26/330 (7.88%)	30	40/334 (11.98%)	42	29/333 (8.71%)	36
Respiratory, thoracic and mediastinal disorders
Cough † 1	33/330 (10.00%)	39	38/334 (11.38%)	42	22/333 (6.61%)	23
Dyspnoea † 1	30/330 (9.09%)	30	29/334 (8.68%)	32	24/333 (7.21%)	25
Haemoptysis † 1	12/330 (3.64%)	14	16/334 (4.79%)	22	17/333 (5.11%)	24
Productive cough † 1	11/330 (3.33%)	12	19/334 (5.69%)	20	9/333 (2.70%)	10
Skin and subcutaneous tissue disorders
Alopecia † 1	33/330 (10.00%)	34	36/334 (10.78%)	38	20/333 (6.01%)	20
Pruritus † 1	36/330 (10.91%)	43	30/334 (8.98%)	41	15/333 (4.50%)	18
Rash † 1	63/330 (19.09%)	81	46/334 (13.77%)	58	22/333 (6.61%)	23
Vascular disorders
Hypertension † 1	20/330 (6.06%)	21	9/334 (2.69%)	13	6/333 (1.80%)	9
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

This study also incorporates a China tail, comprising additional patients randomized after the end of the global cohort recruitment. Efficacy and safety of patients randomized in China will be reported at a later date once this separate analysis has been completed.

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):

Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. doi: 10.1200/JCO.22.00975. Epub 2022 Nov 3.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03164616
• Other Study ID Numbers: D419MC00004; 2017-000920-81 ( EudraCT Number )
• First Submitted: May 22, 2017
• First Posted: May 23, 2017
• Results First Submitted: March 11, 2022
• Results First Posted: April 7, 2022
• Last Update Posted: March 5, 2024