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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03164616
Recruitment Status : Recruiting
First Posted : May 23, 2017
Results First Posted : April 7, 2022
Last Update Posted : November 28, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Small Cell Lung Cancer NSCLC
Interventions Drug: Durvalumab
Drug: Tremelimumab
Drug: Abraxane + carboplatin
Drug: Gemcitabine + cisplatin
Drug: Gemcitabine + carboplatin
Drug: Pemetrexed + carboplatin
Drug: Pemetrexed + cisplatin
Enrollment 1193
Recruitment Details Study was conducted in 142 study centers across 18 countries in North and Latin America, Europe, Asia Pacific and Africa. First patient randomized: 27 June 2017. Results are presented for the global cohort at final analysis data cut-offs (DCOs) of 24 July 2019 (Response Evaluation Criteria in Solid Tumors [RECIST]-based endpoints) and 12 March 2021 (all other data). Once global enrollment was complete, enrollment was started in mainland China. Results for the China cohort will be reported later.
Pre-assignment Details Patients were randomized in a stratified manner as per programmed cell death ligand 1 (PD-L1) tumor expression status (PD-L1 tumor cells [TC] ≥50% versus [vs] <50%), disease stage (IVA vs IVB), and histology (non-squamous vs squamous) in a 1:1:1 ratio to receive treatment with tremelimumab + durvalumab combination therapy + standard of care (SoC) chemotherapy (also referred to as T+ D + SoC), durvalumab monotherapy + SoC chemotherapy (also referred to as D + SoC), or SoC chemotherapy alone.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description

During chemotherapy (combination) stage:

Patients received tremelimumab 75 milligrams (mg) + durvalumab 1500 mg combination therapy + SoC chemotherapy via intravenous (IV) infusion every 3 weeks (Q3W) for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion every 4 weeks (Q4W) from Week 12 until progressive disease (PD), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Period Title: Overall Study
Started [1] 338 338 337
Received Treatment 331 335 331
Completed [2] 80 65 40
Not Completed 258 273 297
Reason Not Completed
Death             250             264             279
Lost to Follow-up             2             2             2
Withdrawal by Subject             6             7             16
[1]
Randomized and included in global cohort analysis
[2]
Completed study or ongoing in study at primary completion date (global cohort final analysis DCO of 12 March 2021)
Arm/Group Title T + D + SoC D + SoC SoC Alone Total
Hide Arm/Group Description

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Total of all reporting groups
Overall Number of Baseline Participants 338 338 337 1013
Hide Baseline Analysis Population Description
Global cohort: All patients in the full analysis set (FAS), which included all randomized patients, were included in the baseline analysis. Patients were included in the analysis in the treatment arm to which they were randomized, regardless of the treatment they received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 338 participants 338 participants 337 participants 1013 participants
62.6  (9.43) 63.5  (9.10) 63.1  (9.87) 63.1  (9.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 338 participants 338 participants 337 participants 1013 participants
Female
69
  20.4%
85
  25.1%
89
  26.4%
243
  24.0%
Male
269
  79.6%
253
  74.9%
248
  73.6%
770
  76.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 338 participants 338 participants 337 participants 1013 participants
White
205
  60.7%
182
  53.8%
179
  53.1%
566
  55.9%
Black or African American
8
   2.4%
4
   1.2%
8
   2.4%
20
   2.0%
Asian
99
  29.3%
123
  36.4%
128
  38.0%
350
  34.6%
Native Hawaiian or other Pacific Islander
2
   0.6%
0
   0.0%
0
   0.0%
2
   0.2%
American Indian or Alaska Native
12
   3.6%
17
   5.0%
9
   2.7%
38
   3.8%
Other
12
   3.6%
12
   3.6%
13
   3.9%
37
   3.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 338 participants 338 participants 337 participants 1013 participants
Hispanic or Latino
51
  15.1%
54
  16.0%
55
  16.3%
160
  15.8%
Not Hispanic or Latino
287
  84.9%
284
  84.0%
282
  83.7%
853
  84.2%
Age Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 338 participants 338 participants 337 participants 1013 participants
≥18 to <50
29
   8.6%
27
   8.0%
30
   8.9%
86
   8.5%
≥50 to <65
162
  47.9%
142
  42.0%
146
  43.3%
450
  44.4%
≥65 to <75
112
  33.1%
130
  38.5%
121
  35.9%
363
  35.8%
≥75
35
  10.4%
39
  11.5%
40
  11.9%
114
  11.3%
1.Primary Outcome
Title Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
Hide Description PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity).
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. Analysis of PFS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure.
Arm/Group Title D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 338 337
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(4.7 to 6.5)
4.8
(4.6 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D + SoC, SoC Alone
Comments D + SoC vs SoC alone. A hazard ratio (HR) <1 favors D + SoC to be associated with a longer PFS than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00093
Comments Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.620 to 0.885
Estimation Comments The HR and confidence interval (CI) were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
2.Primary Outcome
Title Overall Survival (OS); D + SoC Compared With SoC Alone
Hide Description OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity).
Time Frame From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. Analysis of OS was assessed as a primary outcome measure for comparison of the D + SoC vs SoC alone treatment arms only. The alternative treatment arm comparisons were assessed as a secondary outcome measure.
Arm/Group Title D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 338 337
Median (95% Confidence Interval)
Unit of Measure: months
13.3
(11.4 to 14.7)
11.7
(10.5 to 13.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D + SoC, SoC Alone
Comments D + SoC vs SoC alone. An HR <1 favors D + SoC to be associated with a longer OS than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07581
Comments Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.724 to 1.016
Estimation Comments The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
3.Secondary Outcome
Title PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
Hide Description PFS (per RECIST 1.1 using BICR assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 338 338 337
Median (95% Confidence Interval)
Unit of Measure: months
6.2
(5.0 to 6.5)
5.5
(4.7 to 6.5)
4.8
(4.6 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T + D + SoC, SoC Alone
Comments T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer PFS than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00031
Comments Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.600 to 0.860
Estimation Comments The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
4.Secondary Outcome
Title OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
Hide Description OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time Frame From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 338 338 337
Median (95% Confidence Interval)
Unit of Measure: months
14.0
(11.7 to 16.1)
13.3
(11.4 to 14.7)
11.7
(10.5 to 13.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection T + D + SoC, SoC Alone
Comments T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer OS than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00304
Comments Analysis was performed using a stratified log-rank test adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using the Breslow approach for handling ties.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.650 to 0.916
Estimation Comments The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
5.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR (per RECIST 1.1 using BICR assessments) was defined as the percentage of patients with at least one visit response of complete response (CR) or partial response (PR). Results are presented for the pre-specified ORR analysis using unconfirmed responses based on BICR.
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. The denominator was a subset of the FAS who had measurable disease at baseline.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 335 330 332
Measure Type: Number
Unit of Measure: percentage of patients
46.3 48.5 33.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D + SoC, SoC Alone
Comments D + SoC vs SoC alone. An odds ratio >1 favors D + SoC compared to SoC alone. Analysis was performed using logistic regression adjusting for PD-L1 tumor expression (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB), with the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
1.382 to 2.619
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T + D + SoC, SoC Alone
Comments T + D + SoC vs SoC alone. An odds ratio >1 favors T + D + SoC compared to SoC alone. Analysis was performed using logistic regression adjusting for PD-L1 tumor expression (TC ≥50% vs TC <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB), with the CI calculated using a profile likelihood approach.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.72
Confidence Interval (2-Sided) 95%
1.260 to 2.367
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Best Objective Response (BoR)
Hide Description The BoR was calculated based on the overall visit responses from each RECIST 1.1 assessment. BOR was defined as the best response a patient had following randomization, but prior to starting any subsequent cancer therapy and up to and including RECIST 1.1 progression or the last evaluable assessment in the absence of RECIST 1.1 progression, as determined by BICR. Categorization of BoR was based on RECIST using the following 'response' categories: CR and PR and the following 'non-response' categories: stable disease (SD) ≥6 weeks, progression (ie, PD) and not evaluable (NE). Results are presented for number (%) of patients in each specified category.
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. The denominator was a subset of the FAS who had measurable disease at baseline.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 335 330 332
Measure Type: Count of Participants
Unit of Measure: Participants
CR
2
   0.6%
3
   0.9%
0
   0.0%
PR
153
  45.7%
157
  47.6%
111
  33.4%
SD ≥6 weeks
120
  35.8%
107
  32.4%
150
  45.2%
PD
48
  14.3%
60
  18.2%
61
  18.4%
NE
12
   3.6%
3
   0.9%
10
   3.0%
7.Secondary Outcome
Title Duration of Response (DoR)
Hide Description DoR (per RECIST 1.1 using BICR assessments) was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response coincided with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of the initial response was defined as the latest of the dates contributing towards the first visit of PR or CR. Results are presented for the pre-specified DoR analysis using unconfirmed responses based on BICR.
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. Only patients with an objective response were included in the analysis.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 155 160 111
Median (Inter-Quartile Range)
Unit of Measure: months
7.4 [1] 
(3.5 to NA)
6.0 [1] 
(3.4 to NA)
4.2
(3.0 to 6.9)
[1]
75th percentile could not be calculated as it was not reached.
8.Secondary Outcome
Title Time From Randomization to Second Progression (PFS2)
Hide Description PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS) or death. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of: objective radiological imaging, symptomatic progression or death.
Time Frame Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The FAS included all randomized patients.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 338 338 337
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(9.4 to 12.2)
10.2
(9.0 to 11.5)
9.4
(8.6 to 10.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection D + SoC, SoC Alone
Comments D + SoC vs SoC alone. An HR <1 favors D + SoC to be associated with a longer PFS2 than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.666 to 0.928
Estimation Comments The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection T + D + SoC, SoC Alone
Comments T + D + SoC vs SoC alone. An HR <1 favors T + D + SoC to be associated with a longer PFS2 than SoC alone.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.632 to 0.883
Estimation Comments The HR and CI were estimated from a stratified Cox proportional hazards model adjusting for PD-L1 (TC ≥50% vs <50%), histology (squamous vs non-squamous) and disease stage (IVA vs IVB) and using Efron method to control for ties.
9.Secondary Outcome
Title Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
Hide Description To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The PK analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol for whom any post-dose PK data were available and without any protocol deviations that would significantly affect the PK analyses. PK for durvalumab was performed for the T + D + SoC and D + SoC treatment arms only.
Arm/Group Title T + D + SoC D + SoC
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 327 330
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms/milliliter (μg/mL)
Week 0 Number Analyzed 286 participants 303 participants
418.80
(164.20%)
505.01
(48.76%)
Week 3 Number Analyzed 284 participants 285 participants
82.08
(84.38%)
91.53
(100.58%)
Week 12 Number Analyzed 218 participants 226 participants
195.62
(58.65%)
212.11
(60.37%)
Follow-up (3 months) Number Analyzed 59 participants 53 participants
13.42
(166.36%)
16.06
(249.88%)
10.Secondary Outcome
Title PK of Tremelimumab; Peak and Trough Serum Concentrations
Hide Description To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.
Time Frame Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The PK analysis set included all patients who received at least 1 dose of durvalumab or tremelimumab per the protocol for whom any post-dose PK data were available and without any protocol deviations that would significantly affect the PK analyses. PK for tremelimumab was performed for the T + D + SoC treatment arm only.
Arm/Group Title T + D + SoC
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 327
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Week 0 Number Analyzed 294 participants
23.17
(65.62%)
Week 3 Number Analyzed 285 participants
4.16
(80.83%)
Week 12 Number Analyzed 183 participants
7.82
(75.68%)
Follow-up (3 months) Number Analyzed 105 participants
0.86
(87.65%)
11.Secondary Outcome
Title Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
Hide Description Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against durvalumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples.
Time Frame Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The ADA evaluable patients included those in the safety analysis set with non-missing baseline ADA sample and at least 1 post-baseline ADA sample. ADA for durvalumab was performed for the T + D + SoC and D + SoC treatment arms only. The denominator was durvalumab ADA evaluable patients.
Arm/Group Title T + D + SoC D + SoC
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 286 285
Measure Type: Count of Participants
Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)
42
  14.7%
33
  11.6%
Treatment-emergent ADA positive (ADA incidence)
29
  10.1%
19
   6.7%
Treatment-boosted ADA
2
   0.7%
1
   0.4%
Treatment-induced ADA (ADA positive post-baseline only)
27
   9.4%
18
   6.3%
ADA positive at baseline only
8
   2.8%
13
   4.6%
ADA positive post-baseline and positive at baseline
7
   2.4%
2
   0.7%
Persistently positive
8
   2.8%
7
   2.5%
Transiently positive
26
   9.1%
13
   4.6%
nAb positive at any visit
3
   1.0%
3
   1.1%
12.Secondary Outcome
Title Number of Patients With ADA Response to Tremelimumab
Hide Description Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against tremelimumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples.
Time Frame Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).
Hide Outcome Measure Data
Hide Analysis Population Description
Global cohort: The ADA evaluable patients included those in the safety analysis set with non-missing baseline ADA sample and at least 1 post-baseline ADA sample. ADA for tremelimumab was performed for the T + D + SoC treatment arm only. The denominator was tremelimumab ADA evaluable patients.
Arm/Group Title T + D + SoC
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 278
Measure Type: Count of Participants
Unit of Measure: Participants
ADA positive at any visit (ADA prevalence)
44
  15.8%
Treatment-emergent ADA positive (ADA incidence)
38
  13.7%
Treatment-boosted ADA
3
   1.1%
Treatment-induced ADA (ADA positive post-baseline only)
35
  12.6%
ADA positive at baseline only
4
   1.4%
ADA positive post-baseline and positive at baseline
5
   1.8%
Persistently positive
22
   7.9%
Transiently positive
18
   6.5%
nAb positive at any visit
31
  11.2%
13.Secondary Outcome
Title Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)
Hide Description The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
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Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. For QLQ-C30 function scales and global health status/HRQoL, only patients with baseline scores ≥10 (and with data available) were included in the analysis. For QLQ-C30 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 325 326 321
Median (95% Confidence Interval)
Unit of Measure: months
QLQ-C30 Global Health Status / HRQoL Number Analyzed 319 participants 321 participants 318 participants
8.3
(6.4 to 10.2)
7.8
(6.5 to 9.5)
5.6
(4.4 to 7.5)
QLQ-C30 Physical Functioning Number Analyzed 323 participants 325 participants 320 participants
7.7
(5.9 to 9.4)
8.3
(6.6 to 10.0)
5.3
(4.2 to 6.5)
QLQ-C30 Role Functioning Number Analyzed 314 participants 313 participants 304 participants
6.6
(5.4 to 8.3)
7.4
(5.8 to 9.3)
4.8
(3.6 to 6.2)
QLQ-C30 Cognitive Functioning Number Analyzed 323 participants 323 participants 318 participants
7.6
(6.1 to 9.7)
7.4
(5.6 to 9.3)
5.8
(4.6 to 7.5)
QLQ-C30 Emotional Functioning Number Analyzed 322 participants 322 participants 315 participants
8.5
(6.6 to 11.3)
9.5
(7.4 to 12.0)
7.5
(5.8 to 11.0)
QLQ-C30 Social Functioning Number Analyzed 320 participants 319 participants 314 participants
6.4
(5.6 to 9.4)
7.1
(5.0 to 9.6)
5.7
(4.6 to 7.4)
QLQ-C30 Fatigue Number Analyzed 317 participants 318 participants 314 participants
3.7
(2.8 to 5.0)
3.8
(2.9 to 4.9)
2.8
(2.1 to 3.7)
QLQ-C30 Pain Number Analyzed 316 participants 311 participants 298 participants
8.9
(6.2 to 10.9)
6.5
(5.6 to 8.6)
5.7
(4.6 to 7.2)
QLQ-C30 Nausea / Vomiting Number Analyzed 322 participants 322 participants 319 participants
7.8
(5.6 to 10.0)
5.6
(4.1 to 6.6)
5.6
(4.2 to 7.5)
QLQ-C30 Dyspnea Number Analyzed 310 participants 310 participants 301 participants
7.9
(5.8 to 9.8)
6.9
(5.8 to 8.9)
6.7
(5.5 to 8.8)
QLQ-C30 Insomnia Number Analyzed 311 participants 304 participants 301 participants
8.3
(6.4 to 10.4)
7.4
(5.6 to 9.8)
5.8
(4.2 to 7.2)
QLQ-C30 Appetite Loss Number Analyzed 308 participants 316 participants 305 participants
7.2
(5.7 to 9.4)
7.2
(4.7 to 8.8)
7.0
(5.6 to 9.6)
QLQ-C30 Constipation Number Analyzed 315 participants 314 participants 306 participants
9.2
(6.4 to 12.2)
8.7
(6.5 to 10.0)
6.1
(4.8 to 7.5)
QLQ-C30 Diarrhea Number Analyzed 324 participants 324 participants 320 participants
11.0
(9.3 to 13.6)
9.8
(8.1 to 12.9)
10.8
(9.2 to 15.1)
14.Secondary Outcome
Title Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
Hide Description The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.
Time Frame At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).
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Hide Analysis Population Description
Global cohort: The FAS included all randomized patients. For QLQ-LC13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description:

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

Overall Number of Participants Analyzed 325 326 321
Median (95% Confidence Interval)
Unit of Measure: months
QLQ-LC13 Cough Number Analyzed 302 participants 314 participants 295 participants
9.7
(7.3 to 13.3)
11.0
(8.7 to 13.5)
8.8
(6.8 to 12.3)
QLQ-LC13 Hemoptysis Number Analyzed 325 participants 326 participants 318 participants
17.8
(12.5 to 31.3)
14.0
(10.3 to 21.4)
11.4
(9.3 to 19.3)
QLQ-LC13 Dyspnea Number Analyzed 325 participants 325 participants 316 participants
5.4
(4.2 to 6.4)
5.0
(3.8 to 6.4)
3.6
(2.6 to 4.5)
QLQ-LC13 Pain in Chest Number Analyzed 319 participants 322 participants 309 participants
10.0
(7.7 to 13.3)
9.5
(7.8 to 11.8)
8.6
(6.8 to 11.4)
QLQ-LC13 Pain in Arm or Shoulder Number Analyzed 312 participants 311 participants 310 participants
8.9
(6.6 to 10.9)
8.9
(7.4 to 10.3)
8.8
(6.2 to 12.0)
QLQ-LC13 Pain in Other Parts Number Analyzed 312 participants 314 participants 306 participants
9.7
(6.8 to 12.1)
8.9
(6.8 to 11.2)
5.8
(4.9 to 9.3)
Time Frame Adverse events: from first dose of study treatment until the earlier of 90 days after last dose or the date of first subsequent anticancer therapy. All-cause mortality (death due to any cause): from randomization up to global cohort final analysis DCO (12 March 2021). Maximum timeframe of approximately 45 months.
Adverse Event Reporting Description Safety analysis set included all patients who received at least 1 dose of study treatment (analyzed according to actual treatment received). 1 patient randomized to T + D + SoC arm and 1 patient randomized to D + SoC arm only received SoC and were included in SoC alone arm of the safety analysis set. All-cause mortality was determined for patients in the FAS (analyzed according to randomized treatment arm, regardless of the treatment received). Results are reported for the global cohort only.
 
Arm/Group Title T + D + SoC D + SoC SoC Alone
Hide Arm/Group Description

During chemotherapy (combination) stage:

Patients received tremelimumab 75 mg + durvalumab 1500 mg combination therapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. Patients also received an additional dose of tremelimumab 75 mg (in combination with durvalumab) at Week 16 post-chemotherapy.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received durvalumab 1500 mg monotherapy + SoC chemotherapy via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9).

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Patients then continued to receive durvalumab monotherapy 1500 mg IV infusion Q4W from Week 12 until PD, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q4W from Week 12 until PD, unless contraindicated per the Investigator.

During chemotherapy (combination) stage:

Patients received SoC chemotherapy alone via IV infusion Q3W for 4 doses/cycles (Weeks 0, 3, 6 and 9). Patients could also receive SoC chemotherapy for an additional 2 cycles Q3W on Weeks 12 and 15 if clinically indicated and at the Investigator's discretion before the patient entered follow-up.

The SoC chemotherapy was the Investigator's choice of one of the following regimens: abraxane + carboplatin (squamous and non-squamous patients), pemetrexed + cisplatin or carboplatin (non-squamous patients only), or gemcitabine + cisplatin or carboplatin (squamous patients only).

Post-chemotherapy (maintenance) stage:

Non-squamous patients who received pemetrexed + carboplatin/cisplatin during chemotherapy stage could receive pemetrexed maintenance therapy, given Q3W or Q4W (dependent on Investigator decision and local standards) from Week 12 until PD, unless contraindicated per the Investigator.

All-Cause Mortality
T + D + SoC D + SoC SoC Alone
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   251/338 (74.26%)      265/338 (78.40%)      285/337 (84.57%)    
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T + D + SoC D + SoC SoC Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   146/330 (44.24%)      134/334 (40.12%)      117/333 (35.14%)    
Blood and lymphatic system disorders       
Leukopenia  1  2/330 (0.61%)  3 1/334 (0.30%)  1 1/333 (0.30%)  1
Anaemia  1  18/330 (5.45%)  32 23/334 (6.89%)  30 21/333 (6.31%)  25
Neutropenia  1  4/330 (1.21%)  5 6/334 (1.80%)  8 3/333 (0.90%)  5
Pancytopenia  1  2/330 (0.61%)  2 5/334 (1.50%)  6 3/333 (0.90%)  4
Thrombocytopenia  1  8/330 (2.42%)  8 6/334 (1.80%)  7 3/333 (0.90%)  3
Disseminated intravascular coagulation  1  1/330 (0.30%)  1 0/334 (0.00%)  0 1/333 (0.30%)  1
Febrile neutropenia  1  7/330 (2.12%)  7 5/334 (1.50%)  5 4/333 (1.20%)  4
Cardiac disorders       
Acute coronary syndrome  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Acute myocardial infarction  1  2/330 (0.61%)  2 3/334 (0.90%)  3 1/333 (0.30%)  1
Angina pectoris  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Angina unstable  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Atrial fibrillation  1  2/330 (0.61%)  2 1/334 (0.30%)  1 0/333 (0.00%)  0
Atrial tachycardia  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Autoimmune myocarditis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Bundle branch block left  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cardiac arrest  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cardiac failure  1  2/330 (0.61%)  2 0/334 (0.00%)  0 3/333 (0.90%)  3
Cardiac failure acute  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cardiac failure congestive  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Cardiac tamponade  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Cardiopulmonary failure  1  2/330 (0.61%)  2 0/334 (0.00%)  0 1/333 (0.30%)  1
Coronary artery disease  1  1/330 (0.30%)  1 2/334 (0.60%)  2 0/333 (0.00%)  0
Myocardial infarction  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Pericardial effusion  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Right ventricular failure  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Supraventricular tachycardia  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Tachyarrhythmia  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Ventricular fibrillation  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Ear and labyrinth disorders       
Deafness bilateral  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Deafness unilateral  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Endocrine disorders       
Adrenal insufficiency  1  3/330 (0.91%)  3 2/334 (0.60%)  2 0/333 (0.00%)  0
Diabetes insipidus  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Hypopituitarism  1  2/330 (0.61%)  2 1/334 (0.30%)  1 0/333 (0.00%)  0
Eye disorders       
Cataract  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  2
Gastrointestinal disorders       
Abdominal discomfort  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Abdominal pain upper  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Autoimmune pancreatitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Colitis  1  5/330 (1.52%)  5 3/334 (0.90%)  3 0/333 (0.00%)  0
Diarrhoea  1  8/330 (2.42%)  8 3/334 (0.90%)  4 2/333 (0.60%)  2
Diverticular perforation  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Duodenal ulcer haemorrhage  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Dysphagia  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Enteritis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Enterocolitis  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Faecaloma  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Gastric ulcer  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Gastric ulcer haemorrhage  1  1/330 (0.30%)  1 0/334 (0.00%)  0 1/333 (0.30%)  1
Gastric ulcer perforation  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Gastritis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Gastrointestinal haemorrhage  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Gastrointestinal inflammation  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Inguinal hernia  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Intestinal obstruction  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Mesenteric vein thrombosis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Nausea  1  2/330 (0.61%)  2 1/334 (0.30%)  2 2/333 (0.60%)  2
Oesophageal obstruction  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Oesophageal stenosis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Oesophagitis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Pancreatitis  1  2/330 (0.61%)  2 0/334 (0.00%)  0 1/333 (0.30%)  1
Peptic ulcer  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Small intestinal obstruction  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/330 (0.30%)  1 1/334 (0.30%)  1 1/333 (0.30%)  1
Vomiting  1  2/330 (0.61%)  2 2/334 (0.60%)  2 0/333 (0.00%)  0
General disorders       
Asthenia  1  1/330 (0.30%)  1 2/334 (0.60%)  2 2/333 (0.60%)  2
Cardiac death  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Death  1  3/330 (0.91%)  3 6/334 (1.80%)  6 1/333 (0.30%)  1
Face oedema  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Fatigue  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
General physical health deterioration  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Malaise  1  0/330 (0.00%)  0 1/334 (0.30%)  2 0/333 (0.00%)  0
Oedema peripheral  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Pyrexia  1  8/330 (2.42%)  8 1/334 (0.30%)  1 1/333 (0.30%)  1
Sudden death  1  1/330 (0.30%)  1 3/334 (0.90%)  3 0/333 (0.00%)  0
Hepatobiliary disorders       
Autoimmune hepatitis  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Cholangitis  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Cholecystitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Drug-induced liver injury  1  3/330 (0.91%)  3 0/334 (0.00%)  0 0/333 (0.00%)  0
Hepatic failure  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Hepatitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Immune-mediated hepatitis  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Immune system disorders       
Anaphylactic reaction  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Drug hypersensitivity  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Haemophagocytic lymphohistiocytosis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Hypersensitivity  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Infections and infestations       
Abscess oral  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Acute hepatitis B  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Appendicitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Arthritis bacterial  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Bronchitis  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Bronchitis bacterial  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
COVID-19  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
COVID-19 pneumonia  1  1/330 (0.30%)  1 1/334 (0.30%)  1 1/333 (0.30%)  1
Candida pneumonia  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cellulitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 3/333 (0.90%)  4
Chikungunya virus infection  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Cystitis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cytomegalovirus colitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Device related infection  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Diarrhoea infectious  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Disseminated tuberculosis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Empyema  1  2/330 (0.61%)  2 1/334 (0.30%)  1 1/333 (0.30%)  1
Encephalitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Encephalitis viral  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Enterocolitis infectious  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Gastroenteritis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Gastroenteritis viral  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Herpes zoster  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Infection  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Influenza  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Lower respiratory tract infection  1  1/330 (0.30%)  1 2/334 (0.60%)  2 2/333 (0.60%)  2
Neutropenic sepsis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 2/333 (0.60%)  3
Nosocomial infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Ophthalmic herpes zoster  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Oral candidiasis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Perirectal abscess  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Pharyngitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Pleural infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Pneumonia  1  36/330 (10.91%)  42 21/334 (6.29%)  23 16/333 (4.80%)  17
Pneumonia bacterial  1  1/330 (0.30%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Pneumonia klebsiella  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Postoperative wound infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Pulmonary sepsis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Pyelonephritis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Respiratory tract infection  1  3/330 (0.91%)  4 0/334 (0.00%)  0 0/333 (0.00%)  0
Sepsis  1  5/330 (1.52%)  5 2/334 (0.60%)  2 2/333 (0.60%)  2
Septic shock  1  1/330 (0.30%)  1 0/334 (0.00%)  0 1/333 (0.30%)  1
Staphylococcal infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Tracheitis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Tracheobronchitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Upper respiratory tract infection  1  2/330 (0.61%)  2 0/334 (0.00%)  0 2/333 (0.60%)  2
Urinary tract infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 2/333 (0.60%)  2
Vascular device infection  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Viral infection  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Injury, poisoning and procedural complications       
Femoral neck fracture  1  2/330 (0.61%)  2 1/334 (0.30%)  1 0/333 (0.00%)  0
Femur fracture  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Foot fracture  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Hip fracture  1  0/330 (0.00%)  0 2/334 (0.60%)  2 2/333 (0.60%)  2
Infusion related reaction  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Radiation oesophagitis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Road traffic accident  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Spinal compression fracture  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Subdural haematoma  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Subdural haemorrhage  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Toxicity to various agents  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Upper limb fracture  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Investigations       
Alanine aminotransferase increased  1  2/330 (0.61%)  2 3/334 (0.90%)  3 0/333 (0.00%)  0
Aspartate aminotransferase increased  1  0/330 (0.00%)  0 3/334 (0.90%)  3 0/333 (0.00%)  0
Lipase increased  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Neutrophil count decreased  1  0/330 (0.00%)  0 0/334 (0.00%)  0 3/333 (0.90%)  6
Platelet count decreased  1  2/330 (0.61%)  2 2/334 (0.60%)  2 1/333 (0.30%)  1
Transaminases increased  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
White blood cell count decreased  1  0/330 (0.00%)  0 1/334 (0.30%)  1 1/333 (0.30%)  1
Metabolism and nutrition disorders       
Cachexia  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Decreased appetite  1  2/330 (0.61%)  2 1/334 (0.30%)  1 1/333 (0.30%)  1
Dehydration  1  2/330 (0.61%)  2 1/334 (0.30%)  1 2/333 (0.60%)  2
Fluid overload  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Hypercalcaemia  1  1/330 (0.30%)  1 1/334 (0.30%)  1 1/333 (0.30%)  1
Hyperglycaemia  1  2/330 (0.61%)  2 3/334 (0.90%)  3 1/333 (0.30%)  1
Hyperkalaemia  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Hypokalaemia  1  2/330 (0.61%)  2 2/334 (0.60%)  2 0/333 (0.00%)  0
Hyponatraemia  1  3/330 (0.91%)  4 0/334 (0.00%)  0 1/333 (0.30%)  1
Type 1 diabetes mellitus  1  1/330 (0.30%)  2 1/334 (0.30%)  1 0/333 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/330 (0.00%)  0 1/334 (0.30%)  1 1/333 (0.30%)  1
Arthritis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Back pain  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Bone pain  1  0/330 (0.00%)  0 2/334 (0.60%)  2 0/333 (0.00%)  0
Intervertebral disc protrusion  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Mandibular mass  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Muscular weakness  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Musculoskeletal chest pain  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Musculoskeletal pain  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Myositis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Polymyositis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer fatigue  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Cancer pain  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Colon cancer  1  1/330 (0.30%)  1 2/334 (0.60%)  2 0/333 (0.00%)  0
Eyelid naevus  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Neuroendocrine carcinoma metastatic  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Rectal cancer  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Tumour associated fever  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Nervous system disorders       
Brain oedema  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Cerebral infarction  1  3/330 (0.91%)  3 2/334 (0.60%)  2 3/333 (0.90%)  4
Cerebral ischaemia  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Cerebrovascular accident  1  4/330 (1.21%)  4 1/334 (0.30%)  1 1/333 (0.30%)  1
Coordination abnormal  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Dizziness  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Encephalitis autoimmune  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Haemorrhagic stroke  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Headache  1  0/330 (0.00%)  0 0/334 (0.00%)  0 2/333 (0.60%)  2
Hemiplegia  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Ischaemic stroke  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Leukoencephalopathy  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Nervous system disorder  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Polyneuropathy in malignant disease  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Seizure  1  2/330 (0.61%)  2 1/334 (0.30%)  1 1/333 (0.30%)  1
Spinal cord disorder  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Syncope  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Transient ischaemic attack  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Vocal cord paralysis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 2/333 (0.60%)  2
Product Issues       
Device occlusion  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Psychiatric disorders       
Anxiety  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Completed suicide  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Suicide attempt  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  6/330 (1.82%)  6 4/334 (1.20%)  4 1/333 (0.30%)  1
Autoimmune nephritis  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Bladder mass  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Calculus urinary  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Chronic kidney disease  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  2
Glomerulonephritis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Nephritis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Renal failure  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Renal impairment  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Reproductive system and breast disorders       
Uterine haemorrhage  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Atelectasis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Chronic obstructive pulmonary disease  1  2/330 (0.61%)  3 2/334 (0.60%)  2 5/333 (1.50%)  8
Dyspnoea  1  3/330 (0.91%)  3 1/334 (0.30%)  1 2/333 (0.60%)  2
Epistaxis  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Haemoptysis  1  2/330 (0.61%)  2 7/334 (2.10%)  8 3/333 (0.90%)  3
Interstitial lung disease  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Lung infiltration  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Pleural effusion  1  0/330 (0.00%)  0 1/334 (0.30%)  1 2/333 (0.60%)  2
Pneumonia aspiration  1  0/330 (0.00%)  0 2/334 (0.60%)  2 1/333 (0.30%)  1
Pneumonitis  1  6/330 (1.82%)  6 5/334 (1.50%)  5 1/333 (0.30%)  1
Pneumothorax  1  2/330 (0.61%)  2 0/334 (0.00%)  0 0/333 (0.00%)  0
Pulmonary artery thrombosis  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Pulmonary embolism  1  5/330 (1.52%)  5 4/334 (1.20%)  4 9/333 (2.70%)  9
Pulmonary haemorrhage  1  0/330 (0.00%)  0 2/334 (0.60%)  3 3/333 (0.90%)  3
Respiratory failure  1  1/330 (0.30%)  1 1/334 (0.30%)  1 0/333 (0.00%)  0
Skin and subcutaneous tissue disorders       
Drug eruption  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Pemphigoid  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Rash  1  1/330 (0.30%)  1 2/334 (0.60%)  2 0/333 (0.00%)  0
Rash maculo-papular  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Vascular disorders       
Brachiocephalic vein thrombosis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Deep vein thrombosis  1  3/330 (0.91%)  3 0/334 (0.00%)  0 1/333 (0.30%)  1
Embolism  1  1/330 (0.30%)  1 2/334 (0.60%)  2 1/333 (0.30%)  1
Haematoma  1  0/330 (0.00%)  0 0/334 (0.00%)  0 1/333 (0.30%)  1
Hypertensive crisis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Hypotension  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Lymphoedema  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Peripheral artery occlusion  1  0/330 (0.00%)  0 1/334 (0.30%)  1 0/333 (0.00%)  0
Shock  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Shock haemorrhagic  1  0/330 (0.00%)  0 1/334 (0.30%)  1 1/333 (0.30%)  1
Superior vena cava syndrome  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
Vasculitis  1  1/330 (0.30%)  1 0/334 (0.00%)  0 0/333 (0.00%)  0
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
T + D + SoC D + SoC SoC Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   309/330 (93.64%)      302/334 (90.42%)      301/333 (90.39%)    
Blood and lymphatic system disorders       
Leukopenia  1  41/330 (12.42%)  80 32/334 (9.58%)  59 39/333 (11.71%)  80
Anaemia  1  150/330 (45.45%)  213 137/334 (41.02%)  188 146/333 (43.84%)  203
Neutropenia  1  98/330 (29.70%)  177 75/334 (22.46%)  135 77/333 (23.12%)  161
Thrombocytopenia  1  56/330 (16.97%)  83 38/334 (11.38%)  67 54/333 (16.22%)  77
Endocrine disorders       
Hyperthyroidism  1  19/330 (5.76%)  20 20/334 (5.99%)  21 2/333 (0.60%)  3
Hypothyroidism  1  39/330 (11.82%)  42 21/334 (6.29%)  24 4/333 (1.20%)  4
Gastrointestinal disorders       
Abdominal pain  1  19/330 (5.76%)  22 16/334 (4.79%)  19 10/333 (3.00%)  10
Constipation  1  63/330 (19.09%)  85 72/334 (21.56%)  98 79/333 (23.72%)  96
Diarrhoea  1  65/330 (19.70%)  98 57/334 (17.07%)  72 49/333 (14.71%)  66
Nausea  1  136/330 (41.21%)  281 120/334 (35.93%)  258 121/333 (36.34%)  243
Stomatitis  1  17/330 (5.15%)  18 20/334 (5.99%)  25 16/333 (4.80%)  17
Vomiting  1  59/330 (17.88%)  82 51/334 (15.27%)  74 45/333 (13.51%)  80
General disorders       
Asthenia  1  56/330 (16.97%)  67 31/334 (9.28%)  42 39/333 (11.71%)  49
Fatigue  1  81/330 (24.55%)  116 80/334 (23.95%)  119 74/333 (22.22%)  93
Mucosal inflammation  1  17/330 (5.15%)  19 11/334 (3.29%)  15 6/333 (1.80%)  6
Oedema peripheral  1  27/330 (8.18%)  35 23/334 (6.89%)  29 30/333 (9.01%)  34
Pyrexia  1  48/330 (14.55%)  65 30/334 (8.98%)  38 22/333 (6.61%)  30
Infections and infestations       
Upper respiratory tract infection  1  22/330 (6.67%)  32 12/334 (3.59%)  13 18/333 (5.41%)  27
Investigations       
Alanine aminotransferase increased  1  45/330 (13.64%)  66 43/334 (12.87%)  63 44/333 (13.21%)  59
Amylase increased  1  28/330 (8.48%)  47 24/334 (7.19%)  41 16/333 (4.80%)  27
Aspartate aminotransferase increased  1  42/330 (12.73%)  67 36/334 (10.78%)  59 38/333 (11.41%)  51
Blood creatinine increased  1  21/330 (6.36%)  33 12/334 (3.59%)  16 12/333 (3.60%)  21
Gamma-glutamyltransferase increased  1  18/330 (5.45%)  18 17/334 (5.09%)  20 11/333 (3.30%)  11
Lipase increased  1  20/330 (6.06%)  34 12/334 (3.59%)  23 7/333 (2.10%)  12
Neutrophil count decreased  1  39/330 (11.82%)  66 46/334 (13.77%)  96 59/333 (17.72%)  110
Platelet count decreased  1  22/330 (6.67%)  28 19/334 (5.69%)  24 29/333 (8.71%)  35
Weight decreased  1  23/330 (6.97%)  23 29/334 (8.68%)  30 20/333 (6.01%)  24
White blood cell count decreased  1  24/330 (7.27%)  44 21/334 (6.29%)  50 27/333 (8.11%)  53
Metabolism and nutrition disorders       
Decreased appetite  1  92/330 (27.88%)  115 71/334 (21.26%)  89 81/333 (24.32%)  117
Hyperglycaemia  1  18/330 (5.45%)  28 18/334 (5.39%)  25 12/333 (3.60%)  13
Hypokalaemia  1  25/330 (7.58%)  38 11/334 (3.29%)  19 14/333 (4.20%)  20
Hyponatraemia  1  9/330 (2.73%)  12 16/334 (4.79%)  19 18/333 (5.41%)  25
Musculoskeletal and connective tissue disorders       
Arthralgia  1  41/330 (12.42%)  55 28/334 (8.38%)  31 20/333 (6.01%)  23
Back pain  1  25/330 (7.58%)  27 16/334 (4.79%)  21 15/333 (4.50%)  16
Musculoskeletal chest pain  1  18/330 (5.45%)  21 9/334 (2.69%)  9 20/333 (6.01%)  20
Pain in extremity  1  17/330 (5.15%)  20 8/334 (2.40%)  9 8/333 (2.40%)  8
Nervous system disorders       
Dizziness  1  20/330 (6.06%)  22 22/334 (6.59%)  28 9/333 (2.70%)  15
Headache  1  37/330 (11.21%)  49 23/334 (6.89%)  29 24/333 (7.21%)  26
Psychiatric disorders       
Insomnia  1  26/330 (7.88%)  30 40/334 (11.98%)  42 29/333 (8.71%)  36
Respiratory, thoracic and mediastinal disorders       
Cough  1  33/330 (10.00%)  39 38/334 (11.38%)  42 22/333 (6.61%)  23
Dyspnoea  1  30/330 (9.09%)  30 29/334 (8.68%)  32 24/333 (7.21%)  25
Haemoptysis  1  12/330 (3.64%)  14 16/334 (4.79%)  22 17/333 (5.11%)  24
Productive cough  1  11/330 (3.33%)  12 19/334 (5.69%)  20 9/333 (2.70%)  10
Skin and subcutaneous tissue disorders       
Alopecia  1  33/330 (10.00%)  34 36/334 (10.78%)  38 20/333 (6.01%)  20
Pruritus  1  36/330 (10.91%)  43 30/334 (8.98%)  41 15/333 (4.50%)  18
Rash  1  63/330 (19.09%)  81 46/334 (13.77%)  58 22/333 (6.61%)  23
Vascular disorders       
Hypertension  1  20/330 (6.06%)  21 9/334 (2.69%)  13 6/333 (1.80%)  9
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
This study also incorporates a China tail, comprising additional patients randomized after the end of the global cohort recruitment. Efficacy and safety of patients randomized in China will be reported at a later date once this separate analysis has been completed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03164616    
Other Study ID Numbers: D419MC00004
First Submitted: May 22, 2017
First Posted: May 23, 2017
Results First Submitted: March 11, 2022
Results First Posted: April 7, 2022
Last Update Posted: November 28, 2022