A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients - PACIFIC-5

Study identifier:D933YC00001

ClinicalTrials.gov identifier:NCT03706690

EudraCT identifier:2018-002294-22

CTIS identifier:N/A

Recruitment Complete

Official Title

A Phase III, Randomised,Double-Blind,Placebo-Controlled,Study of Durvalumab as Consolidation Therapy in Patients with Locally Advanced,Unresectable NSCLC, Who Have Not Progressed following Definitive, Platinum-Based Chemoradiation Therapy

Medical condition

Carcinoma, Non-Small-Cell Lung

Phase

Phase 3

Healthy volunteers

Study drug

Durvalumab

Sex

All

Actual Enrollment

407

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 27 Nov 2018

Primary Completion Date: 23 Jun 2024

Estimated Study Completion Date: 16 Mar 2027

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Changchun, China, 130000

Location

Research Site

Guangzhou, China, 510100

Location

Research Site

Beijing, China, 100730

Location

Research Site

Wuhan, China, 430030

Location

Research Site

Changsha, China, 410013

Location

Research Site

Yangzhou, China, 225001

Location

Research Site

Hangzhou, China, 310022

Location

Research Site

hangzhou, China, 310006

Arms	Assigned Interventions
Experimental: Durvalumab Therapy Durvalumab (PD-L1 monoclonal antibody)1500 mg every 4 weeks [q4w] intravenously [iv] until clinical progression/deterioration or confirmed radiological progression)	Drug: Durvalumab Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] until clinical progression/ deterioration or confirmed radiological progression. Other Name: MEDI4736
Placebo Comparator: Placebo Therapy Placebo (matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression)	Other: Placebo Matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression Other Name: Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This Phase III double-blind, placebo-controlled study was conducted at 82 investigational sites across 10 countries in participants with locally advanced, unresectable, non-small cell lung cancer (Stage III), who had not progressed following definitive, platinum-based, chemoradiation therapy (CRT).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a screening period (Day -84 to Day -1), randomization (Day 1), treatment period commencing on Day 1 and a survival follow-up period until protocol-specified discontinuation criteria were met. A total of 407 participants were randomized in a 2:1 ratio to receive either durvalumab or placebo in this study. Results are presented up to data cut-off (DCO) date of 23-Jun-2024.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 milligram (mg) via intravenous (IV) infusion on Day 1 and every 4 weeks (Q4W) thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Participant Flow: Overall Study

	Durvalumab	Placebo
STARTED	272	135
Participants who received treatment	271	134
Intent-to-treat (ITT) set	272	135
Modified intent-to-treat (mITT) set	252	129
COMPLETED	0	0
NOT COMPLETED	272	135
Withdrawal by Subject	8	8
Death	143	75
Ongoing at DCO	121	52

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Baseline Measures

	Durvalumab	Placebo	Total
Number of Participants [units: Participants]	272	135	407
Age Continuous [units: years] Mean ± Standard Deviation	61.7 ± 8.33	61.9 ± 7.96	61.7 ± 8.20
Sex: Female, Male [units: participants]
Female	25	18	43
Male	247	117	364
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0	0	0
Asian	197	97	294
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	75	38	113
More than one race	0	0	0
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB) [units: participants]
Hispanic or Latino	5	0	5
Not Hispanic or Latino	267	135	402
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] set) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Primary
Measure Name	Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] set)
Measure Description	The PFS per Response Evaluation Criteria in Solid Tumors 1.1. (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression (PD) or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of >=5 millimeters (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The mITT set included all randomized participants who were without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	252	129
Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] set) [units: months] Median (95% Confidence Interval)	14.0 (10.9 to 18.0)	6.5 (5.4 to 13.8)

Statistical Analysis 1 for Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] set)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.038
Hazard Ratio (HR)^[5]	0.75
95% Confidence Interval	( 0.578 to 0.986 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The hazard ratio and confidence intervals (CIs) were calculated using a stratified Cox proportional hazards model, adjusting for the level of programmed death ligand 1 (PD-L1) expression (PD-L1 <1% versus [vs] PD-L1 >=1%) and prior therapy (concurrent [c]CRT vs sequential [s]CRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis performed using stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	The OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy. Median OS was calculated using the Kaplan-Meier technique.
Time Frame	Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Overall Survival (OS) [units: months] Median (95% Confidence Interval)
mITT set	38.3 (28.9 to 42.8)	32.5 (20.6 to 40.4)
ITT set	38.4 (29.0 to 42.9)	32.5 (20.6 to 40.4)

Statistical Analysis 1 for Overall Survival (OS)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.346
Hazard Ratio (HR)^[5]	0.87
95% Confidence Interval	( 0.656 to 1.166 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For mITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs PD-L1 >=1%) and prior therapy (cCRT vs sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis performed using stratified log-rank test, adjusting for level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Overall Survival (OS)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.346
Hazard Ratio (HR)^[5]	0.87
95% Confidence Interval	( 0.663 to 1.162 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For ITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs PD-L1 >=1%) and prior therapy (cCRT vs sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis performed using stratified log-rank test, adjusting for level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Progression-Free Survival (PFS) (Intent-to-Treat [ITT] set) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Progression-Free Survival (PFS) (Intent-to-Treat [ITT] set)
Measure Description	The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Progression-Free Survival (PFS) (Intent-to-Treat [ITT] set) [units: months] Median (95% Confidence Interval)	14.1 (10.9 to 18.2)	7.4 (5.5 to 13.8)

Statistical Analysis 1 for Progression-Free Survival (PFS) (Intent-to-Treat [ITT] set)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.026
Hazard Ratio (HR)^[5]	0.74
95% Confidence Interval	( 0.575 to 0.966 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs PD-L1>=1%) and prior therapy (cCRT vs sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Analysis performed using stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Percentage of Participants Alive at 24 Months (OS24) [ Time Frame: Month 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Alive at 24 Months (OS24)
Measure Description	OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy. The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months after randomization.
Time Frame	Month 24
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Percentage of Participants Alive at 24 Months (OS24) [units: percentage of participants] Number (95% Confidence Interval)
mITT set	60.7 (54.2 to 66.5)	54.4 (45.2 to 62.7)
ITT set	60.8 (54.7 to 66.5)	54.6 (45.6 to 62.8)

No statistical analysis provided for Percentage of Participants Alive at 24 Months (OS24)

5. Secondary Outcome Measure: Objective Response Rate (ORR) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Objective Response Rate (ORR)
Measure Description	The ORR per RECIST 1.1 using BICR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) based on all participants in the subset of the analysis population including only those participants with measurable disease at baseline per BICR. The CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm. The PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters as long as criteria for PD are not met.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only those participants with measurable disease at baseline per BICR are reported.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	240	127
Objective Response Rate (ORR) [units: percentage of participants]
mITT set	27.6	20.7
ITT set	27.1	19.7

Statistical Analysis 1 for Objective Response Rate (ORR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.128
Odds Ratio (OR)^[5]	1.51
95% Confidence Interval	( 0.891 to 2.607 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For mITT set. The comparison was performed using a logistic regression model, with treatment as a covariate and adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with 95% CI calculated by profile likelihood.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Objective Response Rate (ORR)

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.105
Odds Ratio (OR)^[5]	1.54
95% Confidence Interval	( 0.915 to 2.638 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For ITT set. The comparison was performed using a logistic regression model, with treatment as a covariate and adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with 95% CI calculated by profile likelihood.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Duration of response (DoR) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Duration of response (DoR)
Measure Description	The DoR per RECIST 1.1 using BICR was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. The DoR was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only responders (participants with objective response) are analyzed and reported.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	65	25
Duration of response (DoR) [units: months] Median (95% Confidence Interval)
mITT set	NA (16.6 to NA) ^[1]	37.6 (5.4 to NA) ^[1]
ITT set	NA (20.7 to NA) ^[1]	37.6 (5.4 to NA) ^[1]

No statistical analysis provided for Duration of response (DoR)

7. Secondary Outcome Measure: Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18) [ Time Frame: Months 12 and 18 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18)
Measure Description	The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. The PFS12 and PFS18 were defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by the Investigator at 12 and 18 months, respectively and both were obtained using the algorithm for the RECIST 1.1 site Investigator tumor data.
Time Frame	Months 12 and 18
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18) [units: percentage of participants] Number (95% Confidence Interval)
PFS12, mITT set	53.6 (47.0 to 59.7)	42.7 (33.8 to 51.4)
PFS18, mITT set	43.4 (36.9 to 49.7)	34.1 (25.6 to 42.8)
PFS12, ITT set	54.2 (47.9 to 60.1)	42.5 (33.8 to 51.0)
PFS18, ITT set	44.2 (37.9 to 50.3)	33.4 (25.1 to 41.9)

No statistical analysis provided for Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18)

8. Secondary Outcome Measure: Time From Randomization to Second Progression (PFS2) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Time From Randomization to Second Progression (PFS2)
Measure Description	PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy, or death. The date of the second progression was recorded by the Investigator and defined according to local standard clinical practice and could have involved any of objective radiological imaging, symptomatic progression, or death. Median time to PFS2 was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Time From Randomization to Second Progression (PFS2) [units: months] Median (95% Confidence Interval)
mITT set	26.4 (22.1 to 36.0)	19.5 (14.7 to 28.9)
ITT set	26.2 (22.0 to 34.8)	19.5 (14.3 to 28.9)

Statistical Analysis 1 for Time From Randomization to Second Progression (PFS2)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.275
Hazard Ratio (HR)^[5]	0.86
95% Confidence Interval	( 0.648 to 1.138 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For mITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The analysis was performed using the stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Time From Randomization to Second Progression (PFS2)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.241
Hazard Ratio (HR)^[5]	0.85
95% Confidence Interval	( 0.648 to 1.122 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For ITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The analysis was performed using the stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Time to Death or Distant Metastases (TTDM) [ Time Frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days) ]

Measure Type	Secondary
Measure Name	Time to Death or Distant Metastases (TTDM)
Measure Description	TTDM as per RECIST 1.1 using BICR was defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis was defined as any new lesion that was outside of the radiation field according to RECIST 1.1. Median TTDM was calculated using the Kaplan-Meier technique.
Time Frame	Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	272	135
Time to Death or Distant Metastases (TTDM) [units: months] Median (95% Confidence Interval)
mITT set	42.6 (33.2 to NA) ^[1]	NA (20.3 to NA) ^[1]
ITT set	42.6 (33.2 to NA) ^[1]	NA (20.3 to NA) ^[1]

Statistical Analysis 1 for Time to Death or Distant Metastases (TTDM)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.769
Hazard Ratio (HR)^[5]	1.06
95% Confidence Interval	( 0.726 to 1.578 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For mITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The analysis was performed using the stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Time to Death or Distant Metastases (TTDM)

Groups^[1]	All groups
Method^[3]	Log Rank
P-Value^[4]	0.812
Hazard Ratio (HR)^[5]	1.05
95% Confidence Interval	( 0.726 to 1.539 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	For ITT set. The hazard ratio and CIs were calculated using a stratified Cox proportional hazards model, adjusting for the level of PD-L1 expression (PD-L1 <1% vs. PD-L1 >=1%) and prior therapy (cCRT vs. sCRT), with treatment as the only covariate and ties handled by Efron approach.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	The analysis was performed using the stratified log-rank test, adjusting for the level of PD-L1 expression and prior therapy (cCRT vs. sCRT).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Serum Concentration of Durvalumab [ Time Frame: End of infusion on Cycle 1 Day 1, pre-infusion on Cycles 2 and 4 Day 1 and Month 3 follow-up (each cycle=28 days) ]

Measure Type	Secondary
Measure Name	Serum Concentration of Durvalumab
Measure Description	Blood samples were collected to determine the concentration of durvalumab.
Time Frame	End of infusion on Cycle 1 Day 1, pre-infusion on Cycles 2 and 4 Day 1 and Month 3 follow-up (each cycle=28 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of durvalumab as per protocol for whom any post-dose data were available and who did not violate/deviate from protocol in ways that would significantly have affected the PK analyses. Only those participants with data collected at specified timepoints are reported.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab
Number of Participants Analyzed [units:participants]	249
Serum Concentration of Durvalumab [units: nanogram/milliliter] Mean (Standard Deviation)
Cycle 1 Day 1	511415.541 (222137.0134)
Cycle 2 Day 1	93929.182 (86188.4708)
Cycle 4 Day 1	138752.016 (73792.7522)
Month 3 follow-up	40303.562 (47725.6327)

No statistical analysis provided for Serum Concentration of Durvalumab

11. Secondary Outcome Measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2 and 4 (each cycle=28 days) ]

Measure Type	Secondary
Measure Name	Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
Measure Description	Blood samples were collected to determine the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence was defined as the number of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence was defined as either treatment-induced (post-baseline ADA positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to >=4-fold during the study period). Treatment-induced ADA was defined as ADA positive only post-baseline and not detected at baseline. Persistently positive was defined as having at least 2 post-baseline ADA positive assessments with at least 16 weeks between the first and last positive assessment, or ADA positive at the last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment without fulfilling the conditions for persistently positive.
Time Frame	Pre-dose on Day 1 of Cycles 1, 2 and 4 (each cycle=28 days)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ADA analysis set included all participants who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab
Number of Participants Analyzed [units:participants]	255
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab [units: participants]
ADA positive at any visit (ADA prevalence)	9
Treatment-emergent ADA positive (ADA incidence)	3
ADA positive at both baseline and post-baseline	1
Treatment-induced ADA	3
ADA positive at baseline only	5
Treatment-boosted ADA	0
Persistently positive	0
Transiently positive	4
nAb positive	2

No statistical analysis provided for Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab

12. Secondary Outcome Measure: Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132 [ Time Frame: Baseline (Day 1) and Week 132 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132
Measure Description	Patient reported outcomes for 5 disease related symptoms was assessed using EORTC QLQ-Core 30 (C30) items questionnaire (fatigue, appetite loss) and EORTC QLQ-Lung Cancer module 13 (LC13) (dyspnoea, cough and pain in chest).An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, functional scales, and global health status scale with higher scores on global health status/QoL and functioning scales representing better health status/function, but higher scores on symptom scales/items representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as change from baseline of >=10. Change from baseline in C30: global health status/QoL, physical functioning, fatigue, appetite loss and LC13: dyspnoea, cough and pain in chest are presented.
Time Frame	Baseline (Day 1) and Week 132
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only those participants with data collected at specified timepoints are reported.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab	Placebo
Number of Participants Analyzed [units:participants]	63	22
Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132 [units: units on a scale] Mean (Standard Deviation)
mITT set: EORTC QLQ-C30: Global health status/QoL	78.95 (13.918)	74.21 (17.261)
mITT set: EORTC QLQ-C30: Physical functioning	90.76 (10.216)	92.38 (11.012)
mITT set: EORTC QLQ-C30: Fatigue symptom	10.14 (13.814)	13.76 (18.225)
mITT set: EORTC QLQ-C30: Appetite loss symptom	5.85 (12.791)	3.17 (10.026)
mITT set: EORTC QLQ-LC13: Dyspnoea symptom	15.98 (14.998)	11.11 (12.172)
mITT set: EORTC QLQ-LC13: Cough symptom	16.37 (21.009)	22.22 (21.943)
mITT set: EORTC QLQ-LC13: Pain in chest symptom	9.94 (16.625)	6.35 (13.412)
ITT set: EORTC QLQ-C30: Global health status/QoL	78.70 (13.943)	74.24 (16.846)
ITT set: EORTC QLQ-C30: Physical functioning	90.79 (10.120)	92.73 (10.869)
ITT set: EORTC QLQ-C30: Fatigue symptom	10.93 (14.866)	13.13 (18.026)
ITT set: EORTC QLQ-C30: Appetite loss symptom	5.29 (12.279)	3.03 (9.808)
ITT set: EORTC QLQ-LC13: Dyspnoea symptom	15.17 (14.974)	10.61 (12.112)
ITT set: EORTC QLQ-LC13: Cough symptom	15.87 (21.467)	21.21 (21.932)
ITT set: EORTC QLQ-LC13: Pain in chest symptom	10.05 (17.592)	7.58 (14.298)

No statistical analysis provided for Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132

13. Secondary Outcome Measure: Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Overall Survival, Progression-Free Survival and Objective Response Rate [ Time Frame: Up to 9 years ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Overall Survival, Progression-Free Survival and Objective Response Rate
Measure Description	Blood samples will be collected for clinical biomarker testing and a tumor specimen will be collected as per tumor specimen collection requirements. The specimen will be evaluated by immunohistochemistry to determine the expression of tumor specific antigens and immune markers. The PD-L1 is a biomarker and data for number of participants with its positive status will be presented.
Time Frame	Up to 9 years
Safety Issue?

Results not yet posted. Anticipated Posting Date: Safety Issue: No text entered.

Serious Adverse Events

Time Frame	From time of signature of informed consent up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Additional Description	The Safety analysis set included all participants who received at least 1 dose of study treatment. All-cause mortality was determined for all randomized participants.

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Serious Adverse Events

Durvalumab

Placebo

Total, serious adverse events

# participants affected / at risk

104/271 (38.38%)

45/134 (33.58%)

Gastrointestinal disorders

Oesophageal stenosis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Gastrointestinal disorders

Oesophageal-pulmonary fistula¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

General disorders and administration site conditions

Death¹,^†

# participants affected / at risk

3/271 (1.11%)

0/134 (0.00%)

# events

Cardiac disorders

Acute coronary syndrome¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

3/271 (1.11%)

2/134 (1.49%)

# events

Hepatobiliary disorders

Immune-mediated hepatitis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Arrhythmia¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

5/271 (1.85%)

2/134 (1.49%)

# events

Infections and infestations

COVID-19 pneumonia¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Cardiac disorders

Arteriosclerosis coronary artery¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Infections and infestations

Infectious pleural effusion¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/271 (0.37%)

2/134 (1.49%)

# events

Infections and infestations

Meningitis viral¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Infections and infestations

Pneumocystis jirovecii pneumonia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

21/271 (7.75%)

4/134 (2.99%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

6/271 (2.21%)

2/134 (1.49%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Infections and infestations

Urethritis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Injury, poisoning and procedural complications

Meniscus injury¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹,^†

# participants affected / at risk

14/271 (5.17%)

12/134 (8.96%)

# events

Cardiac disorders

Cardiovascular disorder¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Investigations

Fibrin D dimer increased¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Myocardial injury¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Cardiac disorders

Nodal arrhythmia¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Metabolism and nutrition disorders

Electrolyte imbalance¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Metabolism and nutrition disorders

Gout¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Sinus bradycardia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Musculoskeletal and connective tissue disorders

Intervertebral disc disorder¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Musculoskeletal and connective tissue disorders

Pathological fracture¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal neoplasm¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal squamous cell carcinoma¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Cerebral haemorrhage¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

4/271 (1.48%)

1/134 (0.75%)

# events

Nervous system disorders

Cerebral ischaemia¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Cerebrovascular disorder¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Nervous system disorders

Peripheral motor neuropathy¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Ear and labyrinth disorders

Deafness neurosensory¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Renal and urinary disorders

Chronic kidney disease¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Renal and urinary disorders

Tubulointerstitial nephritis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Renal and urinary disorders

Ureterolithiasis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Atelectasis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial fistula¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

2/271 (0.74%)

2/134 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Immune-mediated lung disease¹,^†

# participants affected / at risk

4/271 (1.48%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

2/271 (0.74%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngeal inflammation¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

15/271 (5.54%)

6/134 (4.48%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

2/271 (0.74%)

0/134 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Tracheal fistula¹,^†

# participants affected / at risk

1/271 (0.37%)

1/134 (0.75%)

# events

Skin and subcutaneous tissue disorders

Eczema¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Skin and subcutaneous tissue disorders

Panniculitis¹,^†

# participants affected / at risk

0/271 (0.00%)

1/134 (0.75%)

# events

Social circumstances

Victim of homicide¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Vascular disorders

Venous thrombosis¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Eye disorders

Pterygium¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Blood and lymphatic system disorders

Myelosuppression¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

Gastrointestinal disorders

Oesophageal fistula¹,^†

# participants affected / at risk

1/271 (0.37%)

0/134 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1

Other Adverse Events

Time Frame	From time of signature of informed consent up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)
Additional Description	The Safety analysis set included all participants who received at least 1 dose of study treatment. All-cause mortality was determined for all randomized participants.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Durvalumab	Participants received durvalumab 1500 mg via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Placebo	Participants received placebo matched to durvalumab via IV infusion on Day 1 and Q4W thereafter until confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Other Adverse Events

Durvalumab

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

223/271 (82.29%)

94/134 (70.15%)

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

18/271 (6.64%)

4/134 (2.99%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

14/271 (5.17%)

5/134 (3.73%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

14/271 (5.17%)

2/134 (1.49%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

30/271 (11.07%)

13/134 (9.70%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

7/271 (2.58%)

9/134 (6.72%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

35/271 (12.92%)

11/134 (8.21%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

41/271 (15.13%)

20/134 (14.93%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

30/271 (11.07%)

15/134 (11.19%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹,^†

# participants affected / at risk

52/271 (19.19%)

27/134 (20.15%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

27/271 (9.96%)

6/134 (4.48%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

22/271 (8.12%)

4/134 (2.99%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

25/271 (9.23%)

5/134 (3.73%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

16/271 (5.90%)

11/134 (8.21%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

14/271 (5.17%)

5/134 (3.73%)

# events

Metabolism and nutrition disorders

Hyperuricaemia¹,^†

# participants affected / at risk

16/271 (5.90%)

4/134 (2.99%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

9/271 (3.32%)

10/134 (7.46%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

23/271 (8.49%)

6/134 (4.48%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

19/271 (7.01%)

6/134 (4.48%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

14/271 (5.17%)

5/134 (3.73%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

32/271 (11.81%)

15/134 (11.19%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

10/271 (3.69%)

7/134 (5.22%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

19/271 (7.01%)

6/134 (4.48%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

14/271 (5.17%)

7/134 (5.22%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

17/271 (6.27%)

6/134 (4.48%)

# events

Endocrine disorders

Hyperthyroidism¹,^†

# participants affected / at risk

33/271 (12.18%)

8/134 (5.97%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

21/271 (7.75%)

9/134 (6.72%)

# events

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

51/271 (18.82%)

10/134 (7.46%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

16/271 (5.90%)

10/134 (7.46%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

14/271 (5.17%)

7/134 (5.22%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
D933YC00001_CSP_Redacted
Download
D933YC00001_CSR synopsis_Redacted
Download
D933YC00001_SAP_Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Astrazeneca Cancer Study Locator Service

1-877-400-4656

AstraZeneca@emergingmed.com

Investigators

Principal Investigator

Yilong Wu

Guangdong General Hospital, Guangdong Lung Cancer Institute

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D933YC00001_CSP_Redacted

D933YC00001_CSR synopsis_Redacted

D933YC00001_SAP_Redacted

Trial Results Summaries