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 1 0
Gastrointestinal disorders    
Oesophageal-pulmonary fistula1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Gastrointestinal disorders    
Pancreatitis1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Gastrointestinal disorders    
Vomiting1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
General disorders and administration site conditions    
Death1, †    
# participants affected / at risk 3/271 (1.11%) 0/134 (0.00%)
# events 3 0
Cardiac disorders    
Acute coronary syndrome1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
General disorders and administration site conditions    
Influenza like illness1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
General disorders and administration site conditions    
Malaise1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 2
Cardiac disorders    
Acute myocardial infarction1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Hepatobiliary disorders    
Cholecystitis1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Hepatobiliary disorders    
Cholecystitis acute1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Angina pectoris1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Hepatobiliary disorders    
Hepatic function abnormal1, †    
# participants affected / at risk 3/271 (1.11%) 2/134 (1.49%)
# events 3 4
Hepatobiliary disorders    
Immune-mediated hepatitis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Arrhythmia1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Infections and infestations    
COVID-191, †    
# participants affected / at risk 5/271 (1.85%) 2/134 (1.49%)
# events 5 2
Infections and infestations    
COVID-19 pneumonia1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Cardiac disorders    
Arteriosclerosis coronary artery1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Infections and infestations    
Gastroenteritis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Infections and infestations    
Infectious pleural effusion1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Atrial fibrillation1, †    
# participants affected / at risk 1/271 (0.37%) 2/134 (1.49%)
# events 1 2
Infections and infestations    
Meningitis viral1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Infections and infestations    
Pneumocystis jirovecii pneumonia1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Infections and infestations    
Pneumonia1, †    
# participants affected / at risk 21/271 (7.75%) 4/134 (2.99%)
# events 23 4
Infections and infestations    
Pneumonia bacterial1, †    
# participants affected / at risk 6/271 (2.21%) 2/134 (1.49%)
# events 7 3
Blood and lymphatic system disorders    
Anaemia1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Cardiac arrest1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Infections and infestations    
Upper respiratory tract infection1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Infections and infestations    
Urethritis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Infections and infestations    
Urinary tract infection1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Injury, poisoning and procedural complications    
Concussion1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Injury, poisoning and procedural complications    
Femur fracture1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 2 0
Cardiac disorders    
Cardiac failure1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Injury, poisoning and procedural complications    
Meniscus injury1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Injury, poisoning and procedural complications    
Radiation pneumonitis1, †    
# participants affected / at risk 14/271 (5.17%) 12/134 (8.96%)
# events 14 12
Cardiac disorders    
Cardiovascular disorder1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Investigations    
Amylase increased1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Cardiac disorders    
Coronary artery disease1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Cardiac disorders    
Myocardial infarction1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Investigations    
Fibrin D dimer increased1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Myocardial injury1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Investigations    
Platelet count decreased1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Cardiac disorders    
Nodal arrhythmia1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 2
Cardiac disorders    
Palpitations1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Metabolism and nutrition disorders    
Electrolyte imbalance1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Metabolism and nutrition disorders    
Gout1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Metabolism and nutrition disorders    
Hypoalbuminaemia1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Sinus bradycardia1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Cardiac disorders    
Sinus tachycardia1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Musculoskeletal and connective tissue disorders    
Intervertebral disc disorder1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Musculoskeletal and connective tissue disorders    
Pathological fracture1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Musculoskeletal and connective tissue disorders    
Spinal osteoarthritis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
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 1 0
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 1 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)    
Laryngeal neoplasm1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
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 0 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)    
Prostate cancer1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)    
Rectal cancer1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
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 1 0
Nervous system disorders    
Cerebral haemorrhage1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Nervous system disorders    
Cerebral infarction1, †    
# participants affected / at risk 4/271 (1.48%) 1/134 (0.75%)
# events 4 1
Nervous system disorders    
Cerebral ischaemia1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Nervous system disorders    
Cerebrovascular accident1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Nervous system disorders    
Cerebrovascular disorder1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Nervous system disorders    
Neuropathy peripheral1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Nervous system disorders    
Peripheral motor neuropathy1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Nervous system disorders    
Transient ischaemic attack1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Ear and labyrinth disorders    
Deafness neurosensory1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Renal and urinary disorders    
Chronic kidney disease1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Renal and urinary disorders    
Tubulointerstitial nephritis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Renal and urinary disorders    
Ureterolithiasis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Respiratory, thoracic and mediastinal disorders    
Atelectasis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Respiratory, thoracic and mediastinal disorders    
Bronchial fistula1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Respiratory, thoracic and mediastinal disorders    
Chronic obstructive pulmonary disease1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 4 2
Respiratory, thoracic and mediastinal disorders    
Cough1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Respiratory, thoracic and mediastinal disorders    
Dyspnoea1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Respiratory, thoracic and mediastinal disorders    
Haemoptysis1, †    
# participants affected / at risk 2/271 (0.74%) 2/134 (1.49%)
# events 2 2
Respiratory, thoracic and mediastinal disorders    
Immune-mediated lung disease1, †    
# participants affected / at risk 4/271 (1.48%) 0/134 (0.00%)
# events 4 0
Respiratory, thoracic and mediastinal disorders    
Interstitial lung disease1, †    
# participants affected / at risk 2/271 (0.74%) 1/134 (0.75%)
# events 2 1
Respiratory, thoracic and mediastinal disorders    
Pharyngeal inflammation1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Respiratory, thoracic and mediastinal disorders    
Pleural effusion1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Respiratory, thoracic and mediastinal disorders    
Pneumonitis1, †    
# participants affected / at risk 15/271 (5.54%) 6/134 (4.48%)
# events 15 6
Respiratory, thoracic and mediastinal disorders    
Pneumothorax1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 2 1
Respiratory, thoracic and mediastinal disorders    
Pulmonary embolism1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Respiratory, thoracic and mediastinal disorders    
Respiratory failure1, †    
# participants affected / at risk 2/271 (0.74%) 0/134 (0.00%)
# events 2 0
Respiratory, thoracic and mediastinal disorders    
Tracheal fistula1, †    
# participants affected / at risk 1/271 (0.37%) 1/134 (0.75%)
# events 1 1
Skin and subcutaneous tissue disorders    
Eczema1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Skin and subcutaneous tissue disorders    
Panniculitis1, †    
# participants affected / at risk 0/271 (0.00%) 1/134 (0.75%)
# events 0 1
Social circumstances    
Victim of homicide1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Vascular disorders    
Venous thrombosis1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Eye disorders    
Pterygium1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
Blood and lymphatic system disorders    
Myelosuppression1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 2 0
Gastrointestinal disorders    
Oesophageal fistula1, †    
# participants affected / at risk 1/271 (0.37%) 0/134 (0.00%)
# events 1 0
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 20 4
General disorders and administration site conditions    
Pyrexia1, †    
# participants affected / at risk 14/271 (5.17%) 5/134 (3.73%)
# events 19 7
Hepatobiliary disorders    
Hepatic function abnormal1, †    
# participants affected / at risk 14/271 (5.17%) 2/134 (1.49%)
# events 15 2
Infections and infestations    
COVID-191, †    
# participants affected / at risk 30/271 (11.07%) 13/134 (9.70%)
# events 31 13
Infections and infestations    
Herpes zoster1, †    
# participants affected / at risk 7/271 (2.58%) 9/134 (6.72%)
# events 8 9
Infections and infestations    
Pneumonia1, †    
# participants affected / at risk 35/271 (12.92%) 11/134 (8.21%)
# events 37 11
Blood and lymphatic system disorders    
Anaemia1, †    
# participants affected / at risk 41/271 (15.13%) 20/134 (14.93%)
# events 57 27
Infections and infestations    
Upper respiratory tract infection1, †    
# participants affected / at risk 30/271 (11.07%) 15/134 (11.19%)
# events 40 20
Injury, poisoning and procedural complications    
Radiation pneumonitis1, †    
# participants affected / at risk 52/271 (19.19%) 27/134 (20.15%)
# events 53 27
Investigations    
Alanine aminotransferase increased1, †    
# participants affected / at risk 27/271 (9.96%) 6/134 (4.48%)
# events 43 8
Investigations    
Amylase increased1, †    
# participants affected / at risk 22/271 (8.12%) 4/134 (2.99%)
# events 44 5
Investigations    
Aspartate aminotransferase increased1, †    
# participants affected / at risk 25/271 (9.23%) 5/134 (3.73%)
# events 48 6
Metabolism and nutrition disorders    
Decreased appetite1, †    
# participants affected / at risk 16/271 (5.90%) 11/134 (8.21%)
# events 17 15
Metabolism and nutrition disorders    
Hyperglycaemia1, †    
# participants affected / at risk 14/271 (5.17%) 5/134 (3.73%)
# events 28 7
Metabolism and nutrition disorders    
Hyperuricaemia1, †    
# participants affected / at risk 16/271 (5.90%) 4/134 (2.99%)
# events 32 12
Metabolism and nutrition disorders    
Hypokalaemia1, †    
# participants affected / at risk 9/271 (3.32%) 10/134 (7.46%)
# events 9 11
Musculoskeletal and connective tissue disorders    
Arthralgia1, †    
# participants affected / at risk 23/271 (8.49%) 6/134 (4.48%)
# events 23 6
Musculoskeletal and connective tissue disorders    
Back pain1, †    
# participants affected / at risk 19/271 (7.01%) 6/134 (4.48%)
# events 20 6
Psychiatric disorders    
Insomnia1, †    
# participants affected / at risk 14/271 (5.17%) 5/134 (3.73%)
# events 15 6
Respiratory, thoracic and mediastinal disorders    
Cough1, †    
# participants affected / at risk 32/271 (11.81%) 15/134 (11.19%)
# events 37 17
Respiratory, thoracic and mediastinal disorders    
Haemoptysis1, †    
# participants affected / at risk 10/271 (3.69%) 7/134 (5.22%)
# events 10 11
Respiratory, thoracic and mediastinal disorders    
Pneumonitis1, †    
# participants affected / at risk 19/271 (7.01%) 6/134 (4.48%)
# events 20 6
Respiratory, thoracic and mediastinal disorders    
Productive cough1, †    
# participants affected / at risk 14/271 (5.17%) 7/134 (5.22%)
# events 16 8
Skin and subcutaneous tissue disorders    
Pruritus1, †    
# participants affected / at risk 17/271 (6.27%) 6/134 (4.48%)
# events 22 6
Endocrine disorders    
Hyperthyroidism1, †    
# participants affected / at risk 33/271 (12.18%) 8/134 (5.97%)
# events 41 8
Skin and subcutaneous tissue disorders    
Rash1, †    
# participants affected / at risk 21/271 (7.75%) 9/134 (6.72%)
# events 27 11
Endocrine disorders    
Hypothyroidism1, †    
# participants affected / at risk 51/271 (18.82%) 10/134 (7.46%)
# events 67 13
Gastrointestinal disorders    
Constipation1, †    
# participants affected / at risk 16/271 (5.90%) 10/134 (7.46%)
# events 17 11
Gastrointestinal disorders    
Diarrhoea1, †    
# participants affected / at risk 14/271 (5.17%) 7/134 (5.22%)
# events 16 10
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:
unchecked 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.
unchecked 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.
unchecked 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]
.