Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)

Non Small Cell Lung Carcinoma NSCLC Clinical Trial

— NEPTUNE  

Official title:

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02542293
• Other study ID #: D419AC00003
• Secondary ID: 2015-002197-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 3, 2015
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.

Description:

Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 953
• Est. completion date: December 31, 2024
• Est. primary completion date: September 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

• Aged at least 18 years

• Documented evidence of Stage IV NSCLC

• No activating EGFR mutation or ALK rearrangement

• No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC

• World Health Organization (WHO) Performance Status of 0 or 1

• No Prior exposure to Immune Mediated Therapy (IMT), including, but not limited to, other antiCTLA4, antiPD1, anti PDL1,or antiPDL2 antibodies, excluding therapeutic anticancer vaccines

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

• Mixed small cell lung cancer and NSCLC histology, sarcomatoid variant

• Brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to start of study treatment.

• Active or prior documented autoimmune or inflammatory disorders (e.g., Crohn's disease, ulcerative colitis)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Carcinoma NSCLC

Intervention

Biological:
• Durvalumab +Tremelimumab

Drug:
• Paclitaxel + carboplatin
Chemotherapy Agents
• Gemcitabine + cisplatin
Chemotherapy Agents
• Gemcitabine + carboplatin
Chemotherapy Agents
• Pemetrexed + cisplatin
Chemotherapy Agent
• Pemetrexed + carboplatin
Chemotherapy Agent

Locations

Country	Name	City	State
Argentina	Research Site	Berazategui
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Córdoba
Argentina	Research Site	La Rioja
Argentina	Research Site	Rosario
Argentina	Research Site	San Salvador de Jujuy
Argentina	Research Site	Santa Rosa
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Fortaleza
Brazil	Research Site	Ijui
Brazil	Research Site	Itajai
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Shumen
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vratza
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Viña del Mar
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Wuhan
Denmark	Research Site	Odense C
Finland	Research Site	Oulu
Finland	Research Site	Tampere
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Holargos, Athens
Greece	Research Site	Ioannina
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	King's Park
Hong Kong	Research Site	Shatin
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Chennai
India	Research Site	Gurgaon
India	Research Site	Karamsad
India	Research Site	New Delhi
Israel	Research Site	Beer Sheva
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Nahariya
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukushima-shi
Japan	Research Site	Habikino-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Iwakuni-shi
Japan	Research Site	Kanazawa
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Mitaka-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Saga-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Tokushima-shi
Japan	Research Site	Ube-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Malaysia	Research Site	Kuching
Mexico	Research Site	Acapulco
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Mérida
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Peru	Research Site	Arequipa
Peru	Research Site	Bellavista
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Baguio City
Philippines	Research Site	Cebu
Philippines	Research Site	Las Pinas City
Philippines	Research Site	Manila
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Poland	Research Site	Bydgoszcz
Poland	Research Site	Kielce
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Mrozy
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wodzislaw Slaski
Portugal	Research Site	Amadora
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Qatar	Research Site	Doha
Romania	Research Site	Suceava
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Sweden	Research Site	Eskilstuna
Sweden	Research Site	Linköping
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Ukraine	Research Site	Chernivts?
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kapitanivka Village
Ukraine	Research Site	Kharkiv Region
Ukraine	Research Site	Kirovohrad
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Lyutizh
Ukraine	Research Site	Odesa
Ukraine	Research Site	Sumy
Ukraine	Research Site	Uzhhorod
Ukraine	Research Site	Vinnytsia
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Taunton
United Kingdom	Research Site	Wirral
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Canton	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	East Setauket	New York
United States	Research Site	Florham Park	New Jersey
United States	Research Site	Fresh Meadows	New York
United States	Research Site	Houston	Texas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Poughkeepsie	New York
United States	Research Site	San Diego	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Stony Brook	New York
United States	Research Site	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  China,  Denmark,  Finland,  Greece,  Hong Kong,  India,  Israel,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Qatar,  Romania,  Russian Federation,  Saudi Arabia,  Singapore,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) =20 Mutations Per Megabase (Mut/Mb) Analysis Set	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 was 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.	From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
Primary	OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set	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 was 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.	From baseline (Day 1, Week 0) until death due to any cause, assessed up to the China cohort DCO date (a maximum of approximately 44 months).
Secondary	OS; Global Cohort: bTMB =16 Mut/Mb, bTMB =12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB =14 Mut/Mb, tTMB =12 Mut/Mb, tTMB =10 Mut/Mb, and tTMB =8 Mut/Mb Analysis Sets	OS was defined as time from 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 time of analysis was censored based on last recorded date on which participant was known to be alive.; bTMB =16 mut/Mb, bTMB =12 mut/Mb and bTMB <20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =16 mut/Mb, =12 mut/Mb and <20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available.; tTMB analysis sets are defined same as the bTMB analysis sets.	From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
Secondary	OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) =25%, and PD-L1 TC =50% Analysis Sets	The OS was defined as time from 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 was censored based on last recorded date on which participant was known to be alive.; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.; PD-L1 TC =25% and PD-L1 TC =50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC =25% and TC =50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.	From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort.
Secondary	Progression-Free Survival (PFS); Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, bTMB =12 Mut/Mb, tTMB =14 Mut/Mb, tTMB =12 Mut/Mb, tTMB =10 Mut/Mb, and tTMB =8 Mut/Mb Analysis Sets	The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.; tTMB =14 mut/Mb, tTMB =12 mut/Mb, tTMB =10 mut/Mb and tTMB =8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was =14 mut/Mb, =12 mut/Mb, =10 mut/Mb and =8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Secondary	PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC =25%, and PD-L1 TC =50% Analysis Sets	PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).; PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: FAS included all randomized participants prior to end of global recruitment.; China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses.; PD-L1 TC =25% and PD-L1 TC =50% analysis sets included subset of participants in FAS whose PD-L1 status was TC =25% and TC =50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Secondary	Objective Response Rate (ORR); Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, bTMB =12 Mut/Mb, tTMB =14 Mut/Mb, tTMB =12 Mut/Mb, tTMB =10 Mut/Mb, and tTMB =8 Mut/Mb Analysis Sets	The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD.; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.; tTMB =14 mut/Mb, tTMB =12 mut/Mb, tTMB =10 mut/Mb and tTMB =8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was =14 mut/Mb, =12 mut/Mb, =10 mut/Mb and =8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Secondary	ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC =25%, and PD-L1 TC =50% Analysis Sets	The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD.; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.; PD-L1 TC =25% and PD-L1 TC =50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC =25% and TC =50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Secondary	Duration of Response (DoR); Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, and bTMB =12 Mut/Mb Analysis Sets	DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1).; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Secondary	DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets	DoR (per RECIST 1.1 using Investigator 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 PD (ie, date of PFS event or censoring - date of first response + 1).; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Secondary	Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, and bTMB =12 Mut/Mb Analysis Sets	The APF12 was defined as the percentage of participants who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary	APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets	The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary	Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, and bTMB =12 Mut/Mb Analysis Sets	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, or death (ie, date of PFS2 event or censoring - date of randomization + 1).; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
Secondary	PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets	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, or death (ie, date of PFS2 event or censoring - date of randomization + 1).; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.	Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
Secondary	OS at Months 12, 18 and 24; Global Cohort: bTMB =20 Mut/Mb, bTMB =16 Mut/Mb, and bTMB =12 Mut/Mb Analysis Sets	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).; bTMB =20 mut/Mb, bTMB =16 mut/Mb and bTMB =12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was =20 mut/Mb, =16 mut/Mb and =12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.	Months 12, 18 and 24
Secondary	OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets	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).; PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).; Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.; China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.	Months 12, 18 and 24
Secondary	Serum Concentrations of Durvalumab	Blood samples were collected to determine the serum concentration of durvalumab.	Pre-dose and within 1 hour after end of infusion at Week 0 and 12; pre-dose on Week 24 and at follow-up Month 3
Secondary	Serum Concentrations of Tremelimumab	Blood samples were collected to determine the serum concentration of tremelimumab.	Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3
Secondary	Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab	Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to >=4 fold during the study period. 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 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
Secondary	Number of Participants With ADA Response to Tremelimumab	Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to >=4 fold during the study period. 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 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

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