Trial Outcomes & Findings for Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC) (NCT NCT02453282)

Last Updated: 2025-09-16

Results Overview

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

1118 participants

Primary outcome timeframe

From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Results posted on

2025-09-16

Participant Flow

A total of 194 centers across 17 countries in Asia, Australia, Europe and North America randomized adults with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type advanced or metastatic non-small cell lung cancer in this study. First participant was randomized on 14 August 2015 and final data cut-off date was 04 October 2018.

A total of 1118 participants were randomized in a 1:1:1 ratio in stratified manner as per programmed cell death ligand 1 (PD-L1) tumor expression status (PD-L1 \[tumor cell (TC) \>=25%\] versus (Vs) PD-L1 \[TC \<25%\]) and histology (squamous Vs non-squamous) to receive durvalumab alone, durvalumab + tremelimumab, or standard of care (SoC) chemotherapy.

Participant milestones

Participant milestones
Measure	Durvalumab Monotherapy Participants received durvalumab 20 milligram per kilogram (mg/kg) intravenous (IV) infusion every 4 weeks (Q4W) until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/square meter (m\^2) and carboplatin area under the plasma drug concentration-time curve (AUC) 5 or 6 mg\minute per milliliter (mg\min/mL). 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Overall Study STARTED	374	372	372
Overall Study Received Treatment	369	371	352
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	374	372	372

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab Monotherapy Participants received durvalumab 20 milligram per kilogram (mg/kg) intravenous (IV) infusion every 4 weeks (Q4W) until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/square meter (m\^2) and carboplatin area under the plasma drug concentration-time curve (AUC) 5 or 6 mg\minute per milliliter (mg\min/mL). 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Overall Study Death	275	277	296
Overall Study Lost to Follow-up	1	0	2
Overall Study Withdrawal by Subject	12	10	11
Overall Study Participants ongoing at data cut-off	85	84	62
Overall Study Other	1	1	1

Baseline Characteristics

Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).	Total n=1118 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 10.30 • n=5 Participants	64.3 years STANDARD_DEVIATION 9.52 • n=7 Participants	63.6 years STANDARD_DEVIATION 9.36 • n=5 Participants	63.7 years STANDARD_DEVIATION 9.74 • n=4 Participants
Sex: Female, Male Female	118 Participants n=5 Participants	106 Participants n=7 Participants	122 Participants n=5 Participants	346 Participants n=4 Participants
Sex: Female, Male Male	256 Participants n=5 Participants	266 Participants n=7 Participants	250 Participants n=5 Participants	772 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	13 Participants n=7 Participants	6 Participants n=5 Participants	34 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	359 Participants n=5 Participants	358 Participants n=7 Participants	366 Participants n=5 Participants	1083 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	243 Participants n=5 Participants	249 Participants n=7 Participants	243 Participants n=5 Participants	735 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Asian	125 Participants n=5 Participants	118 Participants n=7 Participants	120 Participants n=5 Participants	363 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Population: The PD-L1 (TC \>=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab monotherapy Vs SoC and durvalumab + tremelimumab Vs SoC reporting groups were analysed for primary outcome measure.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy	16.3 months Interval 12.2 to 20.8	11.9 months Interval 9.0 to 17.7	12.9 months Interval 10.5 to 15.0

PRIMARY outcome

Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs SoC chemotherapy reporting groups were analysed for the primary outcome measure.

The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=162 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy	3.9 months Interval 2.8 to 5.0	5.4 months Interval 4.6 to 5.8	—

SECONDARY outcome

Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab monotherapy reporting groups were analysed for the secondary outcome measure.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy	16.3 months Interval 12.2 to 20.8	11.9 months Interval 9.0 to 17.7	12.9 months Interval 10.5 to 15.0

SECONDARY outcome

Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Population: The PD-L1 (TC \>=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC \>=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, \>=1% TC expressing PD-L1 on the membrane).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
OS; PD-L1 (TC >=1%) Analysis Set Population	14.6 months Interval 10.5 to 17.7	10.9 months Interval 9.1 to 13.5	12.3 months Interval 10.6 to 14.6

SECONDARY outcome

Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Population: The FAS included all randomized participants analyzed on an ITT basis.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
OS; FAS Population	12.3 months Interval 10.1 to 14.9	11.2 months Interval 9.5 to 12.9	11.8 months Interval 10.5 to 13.3

SECONDARY outcome

Population: The PD-L1 (TC \>=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by Ventana PD-L1 (SP263) assay (ie, \>=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab and durvalumab Vs SoC reporting groups were analysed for secondary outcome measure.

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy	4.7 months Interval 3.1 to 6.3	3.9 months Interval 2.8 to 5.0	5.4 months Interval 4.6 to 5.8

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
PFS; PD-L1 (TC >=1%) Analysis Set Population	3.6 months Interval 2.8 to 4.2	2.8 months Interval 2.5 to 3.4	5.5 months Interval 4.9 to 5.7

SECONDARY outcome

Population: The FAS included all randomized participants analyzed on an ITT basis.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
PFS; FAS Population	2.8 months Interval 2.6 to 3.1	2.9 months Interval 2.6 to 3.4	5.4 months Interval 4.8 to 5.6

SECONDARY outcome

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population	35.6 percentage of participants	34.4 percentage of participants	37.7 percentage of participants

SECONDARY outcome

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
ORR; PD-L1 (TC >=1%) Analysis Set Population	26.5 percentage of participants	25.3 percentage of participants	33.6 percentage of participants

SECONDARY outcome

Population: The FAS included all randomized participants analyzed on an ITT basis.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
ORR; FAS Population	22.2 percentage of participants	24.7 percentage of participants	30.1 percentage of participants

SECONDARY outcome

Population: The PD-L1 (TC \>=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC \>=25%) as defined by the Ventana PD-L1 (SP263) assay (ie,\>=25% TC expressing PD-L1 on the membrane). DoR is only analyzed for those participants with a response (including unconfirmed responses).

The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population	NA months Interval 4.9 to NA = Not reached.	NA months Interval 4.2 to NA = Not reached.	4.4 months Interval 2.9 to 7.2

SECONDARY outcome

The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
DoR; PD-L1 (TC >=1%) Analysis Set Population	NA months Interval 5.5 to NA = Not reached.	NA months Interval 5.6 to NA = Not reached.	4.4 months Interval 2.8 to 8.4

SECONDARY outcome

Population: The FAS included all randomized participants analyzed on an ITT basis. DoR is only analyzed for those participants with a response (including unconfirmed responses).

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
DoR; FAS Population	NA months Interval 5.5 to NA = Not reached.	NA months Interval 4.7 to NA = Not reached.	4.3 months Interval 2.8 to 8.4

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population	32.3 percentage of participants Interval 24.8 to 39.9	25.8 percentage of participants Interval 18.9 to 33.1	14.3 percentage of participants Interval 8.4 to 21.7

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population	27.0 percentage of participants Interval 21.6 to 32.6	20.4 percentage of participants Interval 15.7 to 25.5	14.9 percentage of participants Interval 10.2 to 20.5

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

Population: The FAS included all randomized participants analyzed on an ITT basis.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Percentage of Participants APF12; FAS Population	22.5 percentage of participants Interval 18.1 to 27.1	19.8 percentage of participants Interval 15.6 to 24.4	13.8 percentage of participants Interval 9.7 to 18.6

SECONDARY outcome

Timeframe: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population	12.7 months Interval 9.4 to 16.1	10.9 months Interval 7.9 to 14.1	10.4 months Interval 9.0 to 12.5

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=279 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=296 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=289 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
PFS2; PD-L1 (TC >=1%) Analysis Set Population	10.6 months Interval 8.0 to 12.7	9.4 months Interval 7.8 to 11.4	10.5 months Interval 9.4 to 11.7

SECONDARY outcome

Population: The FAS included all randomized participants analyzed on an ITT basis.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=374 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=372 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=372 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
PFS2; FAS Population	9.3 months Interval 7.9 to 10.6	9.8 months Interval 8.8 to 11.4	10.1 months Interval 9.3 to 10.8

SECONDARY outcome

Timeframe: At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.

Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of \>=10.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=163 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=163 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy n=162 Participants Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months EORTC QLQ-C30: Fatigue	1.2 units on a scale Standard Error 1.83	-1.1 units on a scale Standard Error 1.92	10.6 units on a scale Standard Error 2.34
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months EORTC QLQ-C30: Appetite loss	-3.9 units on a scale Standard Error 2.24	2.4 units on a scale Standard Error 2.37	8.0 units on a scale Standard Error 2.83
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months EORTC QLQ-LC13: Dyspnoea	2.3 units on a scale Standard Error 1.51	0.8 units on a scale Standard Error 1.60	5.6 units on a scale Standard Error 1.90
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months EORTC QLQ-LC13: Cough	-11.4 units on a scale Standard Error 1.88	-5.9 units on a scale Standard Error 2.01	-7.1 units on a scale Standard Error 2.54
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months EORTC QLQ-LC13: Chest pain	0.1 units on a scale Standard Error 1.71	1.6 units on a scale Standard Error 1.80	1.7 units on a scale Standard Error 2.04

SECONDARY outcome

Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.

Population: Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the serum concentration of durvalumab.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=361 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=366 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Serum Concentrations of Durvalumab At Week 0: Pre-infusion	NA microgram per milliliter (mcg/mL) Standard Deviation NA NA = Below lower limit of quantification (LLOQ). The LLOQ = 0.05 mcg/mL.	NA microgram per milliliter (mcg/mL) Standard Deviation NA NA = Below LLOQ. The LLOQ = 0.05 mcg/mL.	—
Serum Concentrations of Durvalumab At Week 0: End of infusion	484.5 microgram per milliliter (mcg/mL) Standard Deviation 210.50	444.3 microgram per milliliter (mcg/mL) Standard Deviation 150.29	—
Serum Concentrations of Durvalumab At Week 12: Pre-infusion	139.5 microgram per milliliter (mcg/mL) Standard Deviation 124.98	140.8 microgram per milliliter (mcg/mL) Standard Deviation 146.25	—
Serum Concentrations of Durvalumab At Week 12: End of infusion	625.3 microgram per milliliter (mcg/mL) Standard Deviation 453.8	506.1 microgram per milliliter (mcg/mL) Standard Deviation 231.89	—
Serum Concentrations of Durvalumab At Week 24: Pre-infusion	163.0 microgram per milliliter (mcg/mL) Standard Deviation 170.04	197.0 microgram per milliliter (mcg/mL) Standard Deviation 228.79	—
Serum Concentrations of Durvalumab At Week 24: End of infusion	598.2 microgram per milliliter (mcg/mL) Standard Deviation 344.52	553.2 microgram per milliliter (mcg/mL) Standard Deviation 193.33	—
Serum Concentrations of Durvalumab At follow-up Month 3	49.3 microgram per milliliter (mcg/mL) Standard Deviation 132.54	41.4 microgram per milliliter (mcg/mL) Standard Deviation 131.71	—

SECONDARY outcome

Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.

Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the serum concentration of tremelimumab.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=366 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Serum Concentrations of Tremelimumab At Week 0: End of infusion	22.6 mcg/mL Standard Deviation 14.84	—	—
Serum Concentrations of Tremelimumab At Week 0: Pre-infusion	NA mcg/mL Standard Deviation NA NA = Below LLOQ. The LLOQ = 0.05 mcg/mL.	—	—
Serum Concentrations of Tremelimumab At Week 12: Pre-infusion	4.9 mcg/mL Standard Deviation 4.16	—	—
Serum Concentrations of Tremelimumab At Week 12: End of infusion	24.8 mcg/mL Standard Deviation 10.43	—	—
Serum Concentrations of Tremelimumab At follow-up Month 3	0.5 mcg/mL Standard Deviation 0.42	—	—

SECONDARY outcome

Timeframe: Within 1 hour after end of infusion on infusion day at Week 12.

Blood samples were collected to determine the Cmax\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=361 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=366 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab	625.3 mcg/mL Standard Deviation 453.80	506.1 mcg/mL Standard Deviation 231.89	—

SECONDARY outcome

Timeframe: Within 1 hour after end of infusion on infusion day at Week 12.

Blood samples were collected to determine the Cmax\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=366 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Cmax_ss of Tremelimumab	24.8 mcg/mL Standard Deviation 10.43	—	—

SECONDARY outcome

Timeframe: Pre-dose at Week 12.

Blood samples were collected to determine the Ctrough\_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=361 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=366 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab	139.5 mcg/mL Standard Deviation 124.98	140.8 mcg/mL Standard Deviation 146.25	—

SECONDARY outcome

Timeframe: Pre-dose at Week 12.

Blood samples were collected to determine the Ctrough\_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=366 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Ctrough_ss of Tremelimumab	4.9 mcg/mL Standard Deviation 4.16	—	—

SECONDARY outcome

Timeframe: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing durvalumab baseline ADA and at least one non-missing post-baseline durvalumab ADA result.

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=212 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab n=223 Participants Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab ADA positive at any time	17 Participants	14 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab Treatment-emergent ADA positive	8 Participants	8 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab ADA positive at baseline and post-baseline	3 Participants	1 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab ADA positive at post-baseline only	8 Participants	8 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab ADA positive at baseline only	6 Participants	5 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab Treatment-boosted ADA	0 Participants	0 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab Persistent positive	8 Participants	9 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab Transient positive	3 Participants	0 Participants	—
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab nAb positive at any visit	2 Participants	1 Participants	—

SECONDARY outcome

Timeframe: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

Population: Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing baseline tremelimumab ADA and at least one non-missing post-baseline tremelimumab ADA result.

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Outcome measures

Outcome measures
Measure	Durvalumab Monotherapy n=219 Participants Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	Durvalumab + Tremelimumab Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.	SoC Chemotherapy Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until worsening of disease under investigation, unless specific treatment discontinuation criteria were met. 1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\min/mL. Additional dose of Gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous tumors only). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
Number of Participants With ADA Response to Tremelimumab ADA positive at any time	33 Participants	—	—
Number of Participants With ADA Response to Tremelimumab Treatment-emergent ADA positive	28 Participants	—	—
Number of Participants With ADA Response to Tremelimumab ADA positive at baseline and post-baseline	1 Participants	—	—
Number of Participants With ADA Response to Tremelimumab ADA positive at post-baseline only	28 Participants	—	—
Number of Participants With ADA Response to Tremelimumab ADA positive at baseline only	4 Participants	—	—
Number of Participants With ADA Response to Tremelimumab Treatment-boosted ADA	0 Participants	—	—
Number of Participants With ADA Response to Tremelimumab Persistent positive	25 Participants	—	—
Number of Participants With ADA Response to Tremelimumab Transient positive	4 Participants	—	—
Number of Participants With ADA Response to Tremelimumab nAb positive at any visit	25 Participants	—	—

Adverse Events

Durvalumab Monotherapy

Serious events: 131 serious events

Other events: 335 other events

Deaths: 278 deaths

Durvalumab + Tremelimumab

Serious events: 178 serious events

Other events: 328 other events

Deaths: 278 deaths

SoC Chemotherapy

Serious events: 112 serious events

Other events: 332 other events

Deaths: 297 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: +1 302 885 1180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place