Trial Outcomes & Findings for Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL) (NCT NCT03003962)

Last Updated: 2025-12-24

Results Overview

OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

669 participants

Primary outcome timeframe

From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]

Results posted on

2025-12-24

Participant Flow

This Phase III, open-label, multi-center study was conducted in participants with programmed cell death ligand 1 (PD-L1)- tumor cell (TC) \>= 25% advanced non small-cell lung cancer (NSCLC) at 85 centers in 10 countries (China, Russia, Hungary, Poland, South Korea, Vietnam, Turkey, Australia, Taiwan, and Thailand). First participant was enrolled on 02 January 2017 and last participant was enrolled on 25 January 2019.

Overall 3075 participants were screened at 98 centers in 12 countries. A total of 669 participants were randomized in a 1:1 ratio. Of those, 549 participants fulfilled the criteria for PD-L1 TC \>= 25% low risk of early mortality (LREM).

Participant milestones

Participant milestones
Measure	Durvalumab Participants received durvalumab 20 milligram (mg)/kilogram (kg) via intravenous (IV) infusion every 4 weeks (Q4W) until documented disease progression (PD) or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC Participants received 1 of the following IV infusion treatment combination platinum-based standard of care (SoC) as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/ square meter (m\^2) and carboplatin area under the plasma concentration curve (AUC) 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Overall Study STARTED	335	334
Overall Study PD L1 TC ≥ 25% LREM Analysis Set	278	271
Overall Study PD L1 TC ≥ 50% Analysis Set	247	246
Overall Study PD L1 TC ≥ 50% LREM Analysis Set	207	199
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	334	334

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab Participants received durvalumab 20 milligram (mg)/kilogram (kg) via intravenous (IV) infusion every 4 weeks (Q4W) until documented disease progression (PD) or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC Participants received 1 of the following IV infusion treatment combination platinum-based standard of care (SoC) as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/ square meter (m\^2) and carboplatin area under the plasma concentration curve (AUC) 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Overall Study Withdrawal by Subject	5	17
Overall Study Death	274	277
Overall Study Participants ongoing at DCO	55	40

Baseline Characteristics

Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).	Total n=669 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 9.73 • n=30 Participants	61.9 years STANDARD_DEVIATION 8.71 • n=30 Participants	61.3 years STANDARD_DEVIATION 9.25 • n=60 Participants
Sex: Female, Male Female	67 Participants n=30 Participants	65 Participants n=30 Participants	132 Participants n=60 Participants
Sex: Female, Male Male	268 Participants n=30 Participants	269 Participants n=30 Participants	537 Participants n=60 Participants
Race/Ethnicity, Customized White	73 Participants n=30 Participants	61 Participants n=30 Participants	134 Participants n=60 Participants
Race/Ethnicity, Customized Asian	262 Participants n=30 Participants	273 Participants n=30 Participants	535 Participants n=60 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=30 Participants	6 Participants n=30 Participants	8 Participants n=60 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	333 Participants n=30 Participants	328 Participants n=30 Participants	661 Participants n=60 Participants

PRIMARY outcome

Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]

Population: The FAS included all randomized participants.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Overall Survival (OS)	14.6 months Interval 12.2 to 16.9	12.8 months Interval 10.1 to 14.7

PRIMARY outcome

Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS in Participants With LREM	14.6 months Interval 12.6 to 17.2	15.0 months Interval 13.1 to 16.8

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS in PD-L1 TC >= 50% Analysis Set	14.6 months Interval 12.0 to 17.7	11.8 months Interval 9.8 to 14.7

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

OS is defined as the time from the date of randomization until death due to ay cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS in PD-L1 TC >= 50% LREM Analysis Set	14.9 months Interval 12.6 to 19.0	14.9 months Interval 11.8 to 17.7

SECONDARY outcome

Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months DCO 27 October 2022)

Population: The FAS included all randomized participants.

The PFS (per RECIST 1.1) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). Progression of disease per RECIST 1.1, when either 1 of the criteria met: Target lesion (TL): at least a 20% increase in the sum of diameters of TLs, for reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Non-target lesion (NTL): Unequivocal progression of existing NTLs. It may be due to an important progression in 1 lesion only or in several lesions. In all cases the progression must be clinically significant for the physician to consider changing (or stopping) therapy. New lesions: the presence of 1 or more new lesions was assessed as progression.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	5.4 months Interval 4.2 to 5.7	4.8 months Interval 4.3 to 5.6

SECONDARY outcome

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set	5.5 months Interval 4.4 to 6.4	5.6 months Interval 4.8 to 5.9

SECONDARY outcome

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set	5.6 months Interval 4.7 to 6.5	4.5 months Interval 4.2 to 5.6

SECONDARY outcome

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set	5.7 months Interval 5.3 to 7.0	5.5 months Interval 4.2 to 5.7

SECONDARY outcome

Population: The FAS included all randomized participants who had PD-L1 expression TC \>= 25% with the VENTANA PD-L1 (SP263) assay.

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs). Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment	37.6 percentage of participants Interval 0.324 to 0.43	37.4 percentage of participants Interval 0.322 to 0.429

SECONDARY outcome

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

ORR (per RECIST 1.1 using Investigator assessments)was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set	38.5 percentage of participants Interval 0.327 to 0.445	40.2 percentage of participants Interval 0.343 to 0.463

SECONDARY outcome

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set	42.1 percentage of participants Interval 0.359 to 0.485	40.7 percentage of participants Interval 0.345 to 0.471

SECONDARY outcome

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set	44.0 percentage of participants Interval 0.371 to 0.51	43.7 percentage of participants Interval 0.367 to 0.509

SECONDARY outcome

Population: The FAS included all randomized participants.

DoR (per RECIST 1.1 using Investigator 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 (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.

Outcome measures

Outcome measures
Measure	Durvalumab n=126 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=125 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment	11.9 months Interval 9.7 to 18.7	4.2 months Interval 3.3 to 4.6

SECONDARY outcome

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=107 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=109 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set	11.6 months Interval 8.2 to 15.7	4.2 months Interval 4.0 to 5.4

SECONDARY outcome

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=104 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=100 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set	12.2 months Interval 8.3 to 21.2	4.2 months Interval 3.0 to 4.6

SECONDARY outcome

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=91 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=87 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set	12.2 months Interval 8.2 to 19.7	4.2 months Interval 3.9 to 5.4

SECONDARY outcome

Timeframe: From date of randomization until 12 months

Population: The FAS included all randomized participants.

The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Alive and Progression-Free at 12 Months (APF12)	25.5 percentage of participants Interval 20.8 to 30.4	13.3 percentage of participants Interval 9.6 to 17.5

SECONDARY outcome

Timeframe: From date of randomization until 12 months

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
APF12 in PD-L1 TC >= 25% LREM Analysis Set	24.1 percentage of participants Interval 19.1 to 29.5	16.4 percentage of participants Interval 11.9 to 21.5

SECONDARY outcome

Timeframe: From date of randomization until 12 months

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
APF12 in PD-L1 TC >= 50% Analysis Set	26.1 percentage of participants Interval 20.7 to 31.9	11.7 percentage of participants Interval 7.7 to 16.5

SECONDARY outcome

Timeframe: From date of randomization until 12 months

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
APF12 in PD-L1 TC >= 50% LREM Analysis Set	26.5 percentage of participants Interval 20.5 to 32.8	14.5 percentage of participants Interval 9.6 to 20.4

SECONDARY outcome

Timeframe: Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)

Population: The FAS included all randomized participants who had PD-L1 expression TC \>= 25% with the VENTANA PD-L1 (SP263) assay.

PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Time From Randomization to Second Progression (PFS2)	11.3 months Interval 9.8 to 12.7	9.3 months Interval 8.1 to 10.7

SECONDARY outcome

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS2 in PD-L1 TC >= 25% LREM Analysis Set	11.8 months Interval 10.1 to 12.9	10.9 months Interval 9.3 to 13.1

SECONDARY outcome

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS2 in PD-L1 TC >= 50% Analysis Set	11.3 months Interval 9.7 to 12.9	8.8 months Interval 8.0 to 10.9

SECONDARY outcome

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
PFS2 in PD-L1 TC >= 50% LREM Analysis Set	12.0 months Interval 10.1 to 13.8	10.9 months Interval 8.8 to 13.1

SECONDARY outcome

Timeframe: From date of randomization till 18 months.

Population: The FAS included all randomized participants.

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 18 Months	42.5 percentage of participants Interval 37.1 to 47.7	34.2 percentage of participants Interval 29.0 to 39.4

SECONDARY outcome

Timeframe: From date of randomization till 18 months

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set	43.0 percentage of participants Interval 37.1 to 48.8	41.4 percentage of participants Interval 35.4 to 47.4

SECONDARY outcome

Timeframe: From date of randomization till 18 months

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 18 Months in PD-L1 TC >= 50% Analysis Set	43.2 percentage of participants Interval 36.9 to 49.3	34.9 percentage of participants Interval 28.8 to 41.0

SECONDARY outcome

Timeframe: From date of randomization till 18 months

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set	44.3 percentage of participants Interval 37.4 to 51.0	42.2 percentage of participants Interval 35.2 to 49.1

SECONDARY outcome

Timeframe: From date of randomization till 24 months

Population: The FAS included all randomized participants.

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 24 Months	34.6 percentage of participants Interval 29.5 to 39.7	27.2 percentage of participants Interval 22.4 to 32.1

SECONDARY outcome

Timeframe: From date of randomization till 24 months

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set	34.7 percentage of participants Interval 29.1 to 40.3	32.8 percentage of participants Interval 27.2 to 38.6

SECONDARY outcome

Timeframe: From date of randomization till 24 months

Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=247 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=246 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 24 Months in PD-L1 TC >= 50% Analysis Set	37.0 percentage of participants Interval 31.0 to 43.1	27.0 percentage of participants Interval 21.5 to 32.8

SECONDARY outcome

Timeframe: From date of randomization till 24 months

Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=207 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=199 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set	36.9 percentage of participants Interval 30.3 to 43.5	32.6 percentage of participants Interval 26.1 to 39.3

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The FAS included all randomized participants.

The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=268 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=249 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) Global health status	-0.7 scores on a scale Standard Error 1.19	-7.4 scores on a scale Standard Error 1.27
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) Physical functioning	-3.3 scores on a scale Standard Error 1.23	-6.1 scores on a scale Standard Error 1.30
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) Fatigue	1.4 scores on a scale Standard Error 1.33	7.2 scores on a scale Standard Error 1.43
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) Appetite loss	-1.1 scores on a scale Standard Error 1.39	9.1 scores on a scale Standard Error 1.50

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM. Only data from the participants analyzed were reported.

The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=236 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=208 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Global health status	-1.4 scores on a scale Standard Error 1.23	-7.3 scores on a scale Standard Error 1.31
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Physical functioning	-3.9 scores on a scale Standard Error 1.22	-6.0 scores on a scale Standard Error 1.29
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Fatigue	2.2 scores on a scale Standard Error 1.33	7.7 scores on a scale Standard Error 1.42
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Appetite loss	-0.2 scores on a scale Standard Error 1.43	9.8 scores on a scale Standard Error 1.52

SECONDARY outcome

Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration (a decrease in the function scales or the global health status/ health-related quality of life \[HRQoL\] from baseline of ≥10) that was confirmed at a subsequent visit or death in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.

Outcome measures

Outcome measures
Measure	Durvalumab n=292 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=291 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Time to Deterioration of EORTC QLQ-C30 Global health status	7.3 months Interval 5.5 to 9.1	3.8 months Interval 3.6 to 5.5
Time to Deterioration of EORTC QLQ-C30 Physical functioning	7.4 months Interval 5.6 to 9.8	3.8 months Interval 3.6 to 5.2
Time to Deterioration of EORTC QLQ-C30 Appetite loss	9.2 months Interval 7.3 to 11.4	3.6 months Interval 2.3 to 3.8
Time to Deterioration of EORTC QLQ-C30 Fatigue	4.9 months Interval 3.7 to 7.0	1.8 months Interval 1.6 to 2.6

SECONDARY outcome

Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.

Outcome measures

Outcome measures
Measure	Durvalumab n=253 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=239 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Global health status	7.4 months Interval 5.6 to 9.2	5.5 months Interval 3.7 to 6.5
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Physical functioning	7.4 months Interval 5.6 to 10.1	4.7 months Interval 3.7 to 5.8
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Appetite loss	9.3 months Interval 7.3 to 11.6	3.7 months Interval 2.6 to 5.0
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set Fatigue	5.5 months Interval 3.8 to 7.4	1.8 months Interval 1.6 to 3.3

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.

The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months.

Outcome measures

Outcome measures
Measure	Durvalumab n=274 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=259 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) Cough	-6.4 scores on a scale Standard Error 1.30	-7.9 scores on a scale Standard Error 1.41
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) Dyspnea	2.4 scores on a scale Standard Error 1.24	4.1 scores on a scale Standard Error 1.32
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) Chest pain	-1.0 scores on a scale Standard Error 1.26	-0.2 scores on a scale Standard Error 1.37

SECONDARY outcome

Timeframe: Baseline and 12 months

Outcome measures

Outcome measures
Measure	Durvalumab n=238 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=216 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Dyspnea	2.9 scores on a scale Standard Error 1.28	3.9 scores on a scale Standard Error 1.35
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Cough	-6.6 scores on a scale Standard Error 1.38	-8.6 scores on a scale Standard Error 1.48
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Chest pain	-0.7 scores on a scale Standard Error 1.30	-1.0 scores on a scale Standard Error 1.40

SECONDARY outcome

Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)

Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication.

Outcome measures

Outcome measures
Measure	Durvalumab n=284 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=281 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Time to Deterioration of EORTC QLQ-LC13 Cough	7.5 months Interval 6.4 to 10.1	6.6 months Interval 5.6 to 8.2
Time to Deterioration of EORTC QLQ-LC13 Dyspnea	2.8 months Interval 1.9 to 4.6	3.6 months Interval 2.4 to 3.8
Time to Deterioration of EORTC QLQ-LC13 Chest pain	9.0 months Interval 6.3 to 11.9	6.4 months Interval 4.6 to 7.2

SECONDARY outcome

Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)

Outcome measures

Outcome measures
Measure	Durvalumab n=246 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=233 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Cough	9.2 months Interval 6.4 to 12.3	8.2 months Interval 6.4 to 11.1
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Dyspnea	3.6 months Interval 2.0 to 4.7	3.6 months Interval 2.4 to 3.8
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set Chest pain	9.8 months Interval 6.4 to 12.6	6.6 months Interval 5.8 to 9.2

SECONDARY outcome

Timeframe: From Baseline and until follow-up period of 57 months

Population: The FAS included all randomized participants.

ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported.

Outcome measures

Outcome measures
Measure	Durvalumab n=335 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=334 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Restricted activity, Baseline	267 number of participants	255 number of participants
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Restricted activity, Follow-up Month 57	0 number of participants	2 number of participants

SECONDARY outcome

Timeframe: From Baseline and until follow-up period of 57 months

Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=278 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC n=271 Participants Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set Restricted activity, Baseline	221 number of participants	203 number of participants
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set Restricted activity, Follow-up Month 57	0 number of participants	2 number of participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: The ADA evaluable analysis set included all participants in the safety analysis set who had a non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.

Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.

Outcome measures

Outcome measures
Measure	Durvalumab n=236 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab Treatment-emergent ADA positive	0.8 percentage of participants	—
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab Treatment-boosted ADA	0.4 percentage of participants	—
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab Persistently positive	0 percentage of participants	—
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab Transiently positive	0.8 percentage of participants	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: The ADA evaluable LREM analysis set included all participants in the safety analysis set who had a non-missing baseline ADA and at least 1 non-missing post-baseline ADA result, and identified by a prognostic model developed by AstraZeneca as having LREM.

Outcome measures

Outcome measures
Measure	Durvalumab n=208 Participants Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.	Platinum-based SoC Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met. 1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions. 2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants). 3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants). 4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted). 5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted).
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set Treatment-emergent ADA positive	1.0 percentage of participants	—
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set Treatment-boosted ADA	0.5 percentage of participants	—
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set Persistently positive	0 percentage of participants	—
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set Transiently positive	1.0 percentage of participants	—

Adverse Events

Durvalumab

Serious events: 132 serious events

Other events: 271 other events

Deaths: 274 deaths

Platinum-based SoC

Serious events: 104 serious events

Other events: 294 other events

Deaths: 277 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER