Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)

• ClinicalTrials.gov Identifier: NCT03875235
• Recruitment Status: Active, not recruiting
• First Posted: March 14, 2019
• Results First Posted: April 13, 2023
• Last Update Posted: May 16, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Biliary Tract Neoplasms
• Interventions: Drug: Durvalumab; Drug: Placebo
• Enrollment: 810

Participant Flow

Recruitment Details

The study is active, not recruiting and conducted in 17 countries with 685 patients who were randomized prior to or on 18 December 2020. Results are reported for the study at data cut-off (DCO) 11 August 2021.

Pre-assignment Details

Eligible patients previously untreated for unresectable locally advanced or metastatic Biliary Tract Cancer (BTC) were randomized in a 1:1 ratio with either Durvalumab in combination with Gemcitabine/Cisplatin or Placebo in combination with Gemcitabine/Cisplatin. Randomization was stratified by disease status (initially unresectable versus recurrent) and primary tumor site (IHCC versus EHCC versus GBC).

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Period Title: Overall Study
Started	341	344
Treated	338	342
Completed	0	0
Not Completed	341	344
Reason Not Completed
Ongoing study treatment	63	20
Off treatment	77	91
Withdrawal by Subject	3	10
Death	198	223

Baseline Characteristics

Arm/Group Title		Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin	Total
Arm/Group Description		Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Total of all reporting groups
Overall Number of Baseline Participants		341	344	685
Baseline Analysis Population Description		Baseline analysis was based on all patients in the full analysis set (FAS), which comprised all patients randomized prior to or on 18 December 2020. 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	341 participants	344 participants	685 participants
		62.2 (10.49)	62.6 (10.66)	62.4 (10.57)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age group (years)	Number Analyzed	341 participants	344 participants	685 participants
	< 65 years	181 53.1%	184 53.5%	365 53.3%
	>=65 - < 75 years	122 35.8%	114 33.1%	236 34.5%
	>= 75 years	38 11.1%	46 13.4%	84 12.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	341 participants	344 participants	685 participants
	Female	172 50.4%	168 48.8%	340 49.6%
	Male	169 49.6%	176 51.2%	345 50.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	341 participants	344 participants	685 participants
	American Indian of Alaska Native	0 0.0%	1 0.3%	1 0.1%
	Asian	185 54.3%	201 58.4%	386 56.4%
	Black or African American	8 2.3%	6 1.7%	14 2.0%
	White	131 38.4%	124 36.0%	255 37.2%
	Other	17 5.0%	12 3.5%	29 4.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (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 second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
Time Frame	From date of randomization until death due to any cause. Assessed up to maximum of approximately 27 months (from date of randomization to primary analysis data cut-off)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Median (95% Confidence Interval); Unit of Measure: Months
	12.8; (11.1 to 14.0)	11.5; (10.1 to 12.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Durvalumab + Gemcitabine + Cisplatin, Placebo + Gemcitabine + Cisplatin
	Comments	The 2-sided significance level for OS at the second interim analysis was 3%.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.021
	Comments	The analysis was performed using a stratified log-rank test adjusting for disease status (initially unresectable versus recurrent) and primary tumor location (IHCC versus EHCC versus GBC), and tested at 0.03 significance level.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 97%; 0.64 to 0.99
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazard model adjusting for disease status and primary tumor location.
Other Statistical Analysis		95% CI 0.66 to 0.97

2. Primary Outcome

Title	Overall Survival (OS) Rate at 18 Months
Description	Overall Survival (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 second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
Time Frame	From date of randomization until death due to any cause. Calculated at 18 months using the Kaplan-Meier technique.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	35.1; (29.1 to 41.2)	25.6; (19.9 to 31.7)

3. Primary Outcome

Title	Overall Survival (OS) Rate at 24 Months
Description	Overall Survival (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 second interim analysis was pre-specified after approximately 397 OS events occurred in both arms (59% maturity).
Time Frame	From date of randomization until death due to any cause. Calculated at 24 months using the Kaplan-Meier technique.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	24.9; (17.9 to 32.5)	10.4; (4.7 to 18.8)

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Assessed up to maximum of approximately 27 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Median (95% Confidence Interval); Unit of Measure: Months
	7.2; (6.7 to 7.4)	5.7; (5.6 to 6.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Durvalumab + Gemcitabine + Cisplatin, Placebo + Gemcitabine + Cisplatin
	Comments	The 2-sided significance level for PFS at the second interim analysis was 4.81%.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	The p-value is based on a stratified log-rank test adjusting for disease status (initially unresectable versus recurrent) and primary tumor location (IHCC versus EHCC versus GBC), and tested at 0.0481 significance level.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95.19%; 0.63 to 0.89
	Estimation Comments	The HR and CI were estimated from a stratified Cox proportional hazard model adjusting for disease status and primary tumor location.
Other Statistical Analysis		95% CI 0.63 to 0.89

5. Secondary Outcome

Title	Progression-free Survival (PFS) Rate at 9 Months
Description	PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Calculated at 9 months using the Kaplan-Meier technique.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	34.8; (29.6 to 40.0)	24.6; (20.0 to 29.5)

6. Secondary Outcome

Title	Progression-free Survival (PFS) Rate at 12 Months
Description	PFS based on investigator assessments according to RECIST version 1.1 was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or a measurable increase in a non-target lesion, or the appearance of new lesions. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor assessments every 6 weeks after randomization for the first 24 weeks and then every 8 weeks thereafter until date of RECIST 1.1 defined radiological progressive disease or death. Calculated at 12 months using the Kaplan-Meier technique

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	16.0; (12.0 to 20.6)	6.6; (4.1 to 9.9)

7. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Disease assessments based on investigator assessments were determined by using RECIST version 1.1 guidelines. The ORR was defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions. The PR was defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR was defined as 2 CRs or 2 PRs with no evidence of progression in-between. Patients who discontinued randomized treatment without progression, received a subsequent anti-cancer therapy and then responded were not included as responders for ORR.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Assessed up to maximum of approximately 27 months.

Outcome Measure Data

Analysis Population Description

Full analysis set - subjects with measurable disease at baseline

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	343
Measure Type: Number; Unit of Measure: Percentage of Participants
	26.7	18.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Durvalumab + Gemcitabine + Cisplatin, Placebo + Gemcitabine + Cisplatin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.011
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 1.11 to 2.31
	Estimation Comments	OR and CI were estimated from a stratified CMH test adjusting for disease status and primary tumor location.

8. Secondary Outcome

Title	Duration of Response (DoR)
Description	The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Assessed up to maximum of approximately 27 months.

Outcome Measure Data

Analysis Population Description

Full analysis set - subjects with objective response and measurable disease at baseline

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	91	64
Median (95% Confidence Interval); Unit of Measure: Months
	6.4; (5.9 to 8.1)	6.2; (4.4 to 7.3)

9. Secondary Outcome

Title	Duration of Response (DoR): Percentage Remaining in Response at 9 Months
Description	The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Calculated at 9 months using the Kaplan-Meier technique

Outcome Measure Data

Analysis Population Description

Full analysis set - subjects with objective response and measurable disease at baseline

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	91	64
Measure Type: Number; Unit of Measure: Percentage of Participants
	32.6	25.3

10. Secondary Outcome

Title	Duration of Response (DoR): Percentage Remaining in Response at 12 Months
Description	The DoR was defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments by using RECIST version 1.1 or death in absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1) . A confirmed CR was defined in above outcome measures. The PD was defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. Median DoR was calculated using Kaplan-Meier method.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Calculated at 12 months using the Kaplan-Meier technique

Outcome Measure Data

Analysis Population Description

Full analysis set - subjects with objective response and measurable disease at baseline

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	91	64
Measure Type: Number; Unit of Measure: Percentage of Participants
	26.1	15.0

11. Secondary Outcome

Title	Disease Control Rate (DCR) - Overall
Description	Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR), partial response (PR) or stable disease (SD).
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter. Assessed up to maximum of approximately 27 months.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Unit of Measure: Percentage of Participants
	85.3	82.6

12. Secondary Outcome

Title	Disease Control Rate (DCR) - 24 Weeks
Description	Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 24 or who have stable disease (SD) at least 24 weeks following start of treatment.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Unit of Measure: Percentage of Participants
	57.5	48.3

13. Secondary Outcome

Title	Disease Control Rate (DCR) - 32 Weeks
Description	Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 32 or who have stable disease (SD) at least 32 weeks following start of treatment.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Unit of Measure: Percentage of Participants
	41.9	36.3

14. Secondary Outcome

Title	Disease Control Rate (DCR) - 48 Weeks
Description	Disease control rate based on investigator assessments according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR) or partial response (PR) by week 48 or who have stable disease (SD) at least 48 weeks following start of treatment.
Time Frame	Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter.

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin	Placebo + Gemcitabine + Cisplatin
Arm/Group Description:	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.	Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
Overall Number of Participants Analyzed	341	344
Measure Type: Number; Unit of Measure: Percentage of Participants
	35.2	27.0

Adverse Events

Time Frame	Adverse events: from first dose of study medication up to 90 days after the last dose of study medication or until the initiation of the first subsequent therapy (whichever comes first), up to maximum of approximately 27 months. All-cause mortality (death due to any cause): from randomization up to analysis DCO (11 August 2021). Maximum timeframe of approximately 27 months.
Adverse Event Reporting Description	There were 341 patients randomized to Durvalumab + Gemcitabine + Cisplatin and 344 patients randomized to Placebo + Gemcitabine + Cisplatin (Full Analysis Set). Five of these patients did not receive treatment (resulting in 338 in Durvalumab arm and 342 in Placebo arm for Safety Analysis Set). Hence, the Total numbers at risk for all-cause mortality is 341 (Durvalumab) and 344 (Placebo), while the Total number at Risk by any Serious/Other Adverse Event is 338 (Durvalumab) and 342 (Placebo).
Arm/Group Title	Durvalumab + Gemcitabine + Cisplatin		Placebo + Gemcitabine + Cisplatin
Arm/Group Description	Drug: Durvalumab IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.		Drug: Placebo IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
All-Cause Mortality
	Durvalumab + Gemcitabine + Cisplatin		Placebo + Gemcitabine + Cisplatin
	Affected / at Risk (%)		Affected / at Risk (%)
Total	198/341 (58.06%)		226/344 (65.70%)
Serious Adverse Events
	Durvalumab + Gemcitabine + Cisplatin		Placebo + Gemcitabine + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	160/338 (47.34%)		149/342 (43.57%)
Blood and lymphatic system disorders
Anaemia † 1	12/338 (3.55%)	16	4/342 (1.17%)	4
Bicytopenia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Febrile neutropenia † 1	4/338 (1.18%)	4	5/342 (1.46%)	5
Myelosuppression † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Neutropenia † 1	2/338 (0.59%)	3	3/342 (0.88%)	3
Pancytopenia † 1	2/338 (0.59%)	2	1/342 (0.29%)	1
Thrombocytopenia † 1	3/338 (0.89%)	3	4/342 (1.17%)	4
Cardiac disorders
Acute coronary syndrome † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Angina pectoris † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Atrial fibrillation † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Sinus tachycardia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Ear and labyrinth disorders
Vertigo † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Endocrine disorders
Adrenal insufficiency † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Eye disorders
Cataract † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Optic ischaemic neuropathy † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Gastrointestinal disorders
Abdominal distension † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Abdominal pain † 1	1/338 (0.30%)	1	8/342 (2.34%)	8
Anal fistula † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Ascites † 1	4/338 (1.18%)	5	6/342 (1.75%)	6
Diarrhoea † 1	4/338 (1.18%)	4	5/342 (1.46%)	6
Duodenal obstruction † 1	0/338 (0.00%)	0	2/342 (0.58%)	3
Duodenal stenosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Duodenal ulcer † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Fistula of small intestine † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Gastric perforation † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Gastritis † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Haematochezia † 1	1/338 (0.30%)	2	0/342 (0.00%)	0
Ileus † 1	3/338 (0.89%)	3	3/342 (0.88%)	3
Immune-mediated enterocolitis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Inguinal hernia † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Intestinal obstruction † 1	2/338 (0.59%)	3	0/342 (0.00%)	0
Large intestine perforation † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Melaena † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Nausea † 1	1/338 (0.30%)	1	3/342 (0.88%)	3
Obstruction gastric † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Pancreatitis † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Pancreatitis acute † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Rectal haemorrhage † 1	1/338 (0.30%)	2	0/342 (0.00%)	0
Small intestinal obstruction † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Upper gastrointestinal haemorrhage † 1	5/338 (1.48%)	5	2/342 (0.58%)	2
Vomiting † 1	5/338 (1.48%)	6	5/342 (1.46%)	5
General disorders
Asthenia † 1	1/338 (0.30%)	1	2/342 (0.58%)	2
Death † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Device related thrombosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Fatigue † 1	6/338 (1.78%)	6	4/342 (1.17%)	4
Malaise † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Peripheral swelling † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Pyrexia † 1	13/338 (3.85%)	16	8/342 (2.34%)	8
Sudden death † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Biliary obstruction † 1	6/338 (1.78%)	8	7/342 (2.05%)	8
Biloma rupture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Cholangitis † 1	25/338 (7.40%)	42	17/342 (4.97%)	20
Cholangitis acute † 1	4/338 (1.18%)	5	4/342 (1.17%)	7
Cholecystitis † 1	1/338 (0.30%)	3	4/342 (1.17%)	4
Cholecystitis acute † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Cholestasis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Gallbladder obstruction † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Gallbladder rupture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hepatic cytolysis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hepatic failure † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hepatic function abnormal † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hepatic haemorrhage † 1	1/338 (0.30%)	2	0/342 (0.00%)	0
Hepatitis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hyperbilirubinaemia † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Jaundice † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Jaundice cholestatic † 1	4/338 (1.18%)	4	5/342 (1.46%)	5
Portal vein thrombosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Immune system disorders
Anaphylactic shock † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Infections and infestations
Gastroenteritis escherichia coli † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Infection † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Infectious pleural effusion † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Klebsiella infection † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Liver abscess † 1	1/338 (0.30%)	1	2/342 (0.58%)	2
Lower respiratory tract infection † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Nasopharyngitis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Neutropenic sepsis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Peritonitis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Pneumocystis jirovecii pneumonia † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Pneumonia † 1	6/338 (1.78%)	7	7/342 (2.05%)	8
Pyelonephritis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Sepsis † 1	11/338 (3.25%)	11	9/342 (2.63%)	12
Septic shock † 1	1/338 (0.30%)	1	4/342 (1.17%)	6
Urinary tract infection † 1	6/338 (1.78%)	6	1/342 (0.29%)	1
Abdominal infection † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Abdominal wall abscess † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Abscess intestinal † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Acinetobacter sepsis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Appendicitis † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Arthritis bacterial † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Bacteraemia † 1	1/338 (0.30%)	1	5/342 (1.46%)	5
Biliary abscess † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Biliary sepsis † 1	4/338 (1.18%)	4	2/342 (0.58%)	2
Biliary tract infection † 1	5/338 (1.48%)	7	7/342 (2.05%)	8
Bronchitis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Covid-19 † 1	4/338 (1.18%)	4	2/342 (0.58%)	2
Covid-19 pneumonia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Catheter site infection † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Cellulitis † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Cholangitis infective † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Clostridium difficile infection † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Device related infection † 1	2/338 (0.59%)	3	3/342 (0.88%)	3
Device related sepsis † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Escherichia sepsis † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Gallbladder empyema † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Injury, poisoning and procedural complications
Ankle fracture † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Chemical peritonitis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Fall † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Femoral neck fracture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Femur fracture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Incisional hernia † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Infusion related reaction † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Lower limb fracture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Overdose † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Post procedural complication † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Procedural pain † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Spinal fracture † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Transfusion reaction † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Investigations
Alanine aminotransferase increased † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Blood bilirubin increased † 1	1/338 (0.30%)	1	4/342 (1.17%)	4
Blood creatinine increased † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Liver function test increased † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Neutrophil count decreased † 1	3/338 (0.89%)	4	2/342 (0.58%)	2
Platelet count decreased † 1	4/338 (1.18%)	4	3/342 (0.88%)	3
Metabolism and nutrition disorders
Decreased appetite † 1	3/338 (0.89%)	3	2/342 (0.58%)	2
Diabetic ketoacidosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Gout † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hypercalcaemia † 1	2/338 (0.59%)	3	1/342 (0.29%)	1
Hyperglycaemia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hyperkalaemia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hypoglycaemia † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hypokalaemia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hypomagnesaemia † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Hyponatraemia † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Musculoskeletal and connective tissue disorders
Arthritis † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Back pain † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Immune-mediated arthritis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Polymyositis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Colorectal cancer † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Tumour associated fever † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Tumour pain † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Nervous system disorders
Altered state of consciousness † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Cerebral haemorrhage † 1	2/338 (0.59%)	2	0/342 (0.00%)	0
Cerebral infarction † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Cerebrovascular accident † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Dizziness † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Encephalopathy † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Hepatic encephalopathy † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Ischaemic stroke † 1	4/338 (1.18%)	4	1/342 (0.29%)	1
Product Issues
Device malfunction † 1	2/338 (0.59%)	2	2/342 (0.58%)	3
Device occlusion † 1	0/338 (0.00%)	0	4/342 (1.17%)	4
Stent malfunction † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Psychiatric disorders
Adjustment disorder † 1	0/338 (0.00%)	0	1/342 (0.29%)	2
Confusional state † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Personality change † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Suicide attempt † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Renal and urinary disorders
Acute kidney injury † 1	8/338 (2.37%)	11	4/342 (1.17%)	4
Azotaemia † 1	1/338 (0.30%)	2	0/342 (0.00%)	0
Haematuria † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Nephropathy toxic † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Renal failure † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Asphyxia † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Dyspnoea † 1	0/338 (0.00%)	0	2/342 (0.58%)	2
Hiccups † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Interstitial lung disease † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Obstructive airways disorder † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Pleural effusion † 1	1/338 (0.30%)	1	1/342 (0.29%)	1
Pneumonia aspiration † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Pneumonitis † 1	2/338 (0.59%)	2	2/342 (0.58%)	2
Pneumothorax † 1	0/338 (0.00%)	0	1/342 (0.29%)	2
Pulmonary embolism † 1	6/338 (1.78%)	6	4/342 (1.17%)	4
Pulmonary oedema † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Respiratory failure † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Vascular disorders
Angiopathy † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Arterial thrombosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Deep vein thrombosis † 1	1/338 (0.30%)	1	2/342 (0.58%)	2
Hypertension † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Hypotension † 1	1/338 (0.30%)	1	2/342 (0.58%)	2
Jugular vein thrombosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Peripheral artery thrombosis † 1	1/338 (0.30%)	1	0/342 (0.00%)	0
Thrombosis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
Venous thrombosis † 1	0/338 (0.00%)	0	1/342 (0.29%)	1
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Durvalumab + Gemcitabine + Cisplatin		Placebo + Gemcitabine + Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	326/338 (96.45%)		330/342 (96.49%)
Blood and lymphatic system disorders
Anaemia † 1	159/338 (47.04%)	246	149/342 (43.57%)	246
Leukopenia † 1	20/338 (5.92%)	43	17/342 (4.97%)	34
Neutropenia † 1	106/338 (31.36%)	212	101/342 (29.53%)	204
Thrombocytopenia † 1	42/338 (12.43%)	67	42/342 (12.28%)	76
Endocrine disorders
Hypothyroidism † 1	22/338 (6.51%)	22	11/342 (3.22%)	11
Gastrointestinal disorders
Abdominal pain † 1	46/338 (13.61%)	59	54/342 (15.79%)	62
Abdominal pain upper † 1	35/338 (10.36%)	41	30/342 (8.77%)	35
Constipation † 1	108/338 (31.95%)	133	99/342 (28.95%)	117
Diarrhoea † 1	54/338 (15.98%)	69	47/342 (13.74%)	74
Dyspepsia † 1	21/338 (6.21%)	24	25/342 (7.31%)	26
Nausea † 1	136/338 (40.24%)	211	117/342 (34.21%)	201
Stomatitis † 1	23/338 (6.80%)	29	22/342 (6.43%)	25
Vomiting † 1	59/338 (17.46%)	81	57/342 (16.67%)	84
General disorders
Asthenia † 1	47/338 (13.91%)	76	48/342 (14.04%)	70
Fatigue † 1	87/338 (25.74%)	151	86/342 (25.15%)	123
Oedema peripheral † 1	27/338 (7.99%)	31	17/342 (4.97%)	23
Pyrexia † 1	60/338 (17.75%)	98	49/342 (14.33%)	84
Infections and infestations
Urinary tract infection † 1	18/338 (5.33%)	25	19/342 (5.56%)	20
Investigations
Alanine aminotransferase increased † 1	29/338 (8.58%)	37	34/342 (9.94%)	44
Aspartate aminotransferase increased † 1	23/338 (6.80%)	30	31/342 (9.06%)	39
Blood bilirubin increased † 1	9/338 (2.66%)	10	20/342 (5.85%)	22
Blood creatinine increased † 1	10/338 (2.96%)	12	33/342 (9.65%)	43
Gamma-glutamyltransferase increased † 1	12/338 (3.55%)	15	18/342 (5.26%)	27
Neutrophil count decreased † 1	89/338 (26.33%)	225	105/342 (30.70%)	262
Platelet count decreased † 1	68/338 (20.12%)	126	77/342 (22.51%)	175
Weight decreased † 1	20/338 (5.92%)	20	20/342 (5.85%)	24
White blood cell count decreased † 1	37/338 (10.95%)	78	46/342 (13.45%)	104
Metabolism and nutrition disorders
Decreased appetite † 1	85/338 (25.15%)	102	79/342 (23.10%)	91
Hypokalaemia † 1	28/338 (8.28%)	38	16/342 (4.68%)	24
Hypomagnesaemia † 1	32/338 (9.47%)	48	29/342 (8.48%)	34
Hyponatraemia † 1	22/338 (6.51%)	25	21/342 (6.14%)	23
Musculoskeletal and connective tissue disorders
Arthralgia † 1	20/338 (5.92%)	22	14/342 (4.09%)	15
Back pain † 1	28/338 (8.28%)	32	22/342 (6.43%)	24
Myalgia † 1	15/338 (4.44%)	20	19/342 (5.56%)	22
Nervous system disorders
Dizziness † 1	21/338 (6.21%)	24	16/342 (4.68%)	20
Dysgeusia † 1	20/338 (5.92%)	24	16/342 (4.68%)	22
Headache † 1	23/338 (6.80%)	26	14/342 (4.09%)	18
Psychiatric disorders
Insomnia † 1	32/338 (9.47%)	34	36/342 (10.53%)	36
Respiratory, thoracic and mediastinal disorders
Cough † 1	22/338 (6.51%)	23	18/342 (5.26%)	18
Dyspnoea † 1	22/338 (6.51%)	26	17/342 (4.97%)	20
Skin and subcutaneous tissue disorders
Alopecia † 1	28/338 (8.28%)	30	15/342 (4.39%)	15
Pruritus † 1	38/338 (11.24%)	46	28/342 (8.19%)	30
Rash † 1	38/338 (11.24%)	56	27/342 (7.89%)	34
Rash maculo-papular † 1	18/338 (5.33%)	21	8/342 (2.34%)	9
Vascular disorders
Hypertension † 1	19/338 (5.62%)	31	20/342 (5.85%)	23
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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 Clinical Study Information Center
• Phone: 1-877-240-9479
• EMail: information.center@astrazeneca.com

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03875235
• Other Study ID Numbers: D933AC00001; 2018-004688-30 ( EudraCT Number )
• First Submitted: March 13, 2019
• First Posted: March 14, 2019
• Results First Submitted: August 10, 2022
• Results First Posted: April 13, 2023
• Last Update Posted: May 16, 2024