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

Non-Small-Cell Lung Carcinoma NSCLC Clinical Trial

— MYSTIC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02453282
• Other study ID #: D419AC00001
• Secondary ID: 2015-001279-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 21, 2015
• Est. completion date: December 31, 2024

Study information

• Verified date: April 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 MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy 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 locally advanced or metastatic NSCLC

Description:

Patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1118
• Est. completion date: December 31, 2024
• Est. primary completion date: October 4, 2018
• 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 sensitizing 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 Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are

fulfilled:

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant

2. Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)

3. Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines

4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease]

Related Conditions & MeSH terms

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

Intervention

Biological:
• MEDI4736 (Durvalumab)

• MEDI4736 (Durvalumab)+Tremelimumab

Drug:
• Paclitaxel + Carboplatin
Chemotherapy Agents
• Gemcitabine + Cisplatin
Chemotherapy Agents
• Gemcitabine + Carboplatin
Chemotherapy Agents
• Pemetrexed + Cisplatin
Chemotherapy Agents
• Pemetrexed + Carboplatin
Chemotherapy Agents

Biological:
• Tremelimumab

Locations

Country	Name	City	State
Australia	Research Site	Box Hill
Australia	Research Site	Gosford
Australia	Research Site	Kogarah
Australia	Research Site	Melbourne
Australia	Research Site	Port Macquarie
Australia	Research Site	Southport
Australia	Research Site	St Leonards
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Duffel
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Regina	Saskatchewan
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Sault Ste. Marie	Ontario
Canada	Research Site	St. Catharines	Ontario
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
France	Research Site	Bordeaux Cedex
France	Research Site	Brest Cedex
France	Research Site	Creteil
France	Research Site	Lille
France	Research Site	Lyon Cedex 08
France	Research Site	Marseille cedex
Germany	Research Site	Aachen
Germany	Research Site	Bad Berka
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Freiburg
Germany	Research Site	Gauting
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Hemer
Germany	Research Site	Homburg/Saar
Germany	Research Site	Immenhausen
Germany	Research Site	Löwenstein
Germany	Research Site	Lubeck
Germany	Research Site	Mainz
Germany	Research Site	Münster
Germany	Research Site	Oldenburg
Germany	Research Site	Ulm
Germany	Research Site	Velbert
Germany	Research Site	Würzburg
Hungary	Research Site	Budapest
Hungary	Research Site	Deszk
Hungary	Research Site	Edelény
Hungary	Research Site	Kaposvár
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Székesfehérvár
Italy	Research Site	Genova
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	San Giovanni Rotondo
Italy	Research Site	Siena
Japan	Research Site	Fukushima-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Iwakuni-shi
Japan	Research Site	Izumi-shi
Japan	Research Site	Kanazawa
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Kyoto-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	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Saga-shi
Japan	Research Site	Saitama-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Tokushima-shi
Japan	Research Site	Ube-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokosuka-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Changwon-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jinju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seongnam-Si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Korea, Republic of	Research Site	Ulsan
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Breda
Netherlands	Research Site	Den Bosch
Netherlands	Research Site	Groningen
Netherlands	Research Site	Maastricht
Netherlands	Research Site	Rotterdam
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	A Coruña
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Gerona
Spain	Research Site	Jaén
Spain	Research Site	León
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Switzerland	Research Site	Bellinzona
Switzerland	Research Site	Lausanne
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Tao-Yuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
United States	Research Site	Athens	Georgia
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cleveland	Ohio
United States	Research Site	Fullerton	California
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Jacksonville	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Mineola	New York
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Omaha	Nebraska
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Redondo Beach	California
United States	Research Site	Richmond	Virginia
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Luis Obispo	California
United States	Research Site	Santa Maria	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Summit	New Jersey
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	West Hollywood	California
United States	Research Site	Yuma	Arizona
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi City
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Belgium,  Canada,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy	The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Primary	Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy	The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy	The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	OS; PD-L1 (TC >=1%) Analysis Set Population	The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	OS; FAS Population	The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.	From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy	The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	PFS; PD-L1 (TC >=1%) Analysis Set Population	The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	PFS; FAS Population	The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	ORR; PD-L1 (TC >=1%) Analysis Set Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	ORR; FAS Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population	The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	DoR; PD-L1 (TC >=1%) Analysis Set Population	The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	DoR; FAS Population	The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary	Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary	Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary	Percentage of Participants APF12; FAS Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary	Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary	PFS2; PD-L1 (TC >=1%) Analysis Set Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary	PFS2; FAS Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary	Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months	Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of >=10.	At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.
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, 12 and 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	Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab	Blood samples were collected to determine the Cmax_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Within 1 hour after end of infusion on infusion day at Week 12.
Secondary	Cmax_ss of Tremelimumab	Blood samples were collected to determine the Cmax_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Within 1 hour after end of infusion on infusion day at Week 12.
Secondary	Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab	Blood samples were collected to determine the Ctrough_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Pre-dose at Week 12.
Secondary	Ctrough_ss of Tremelimumab	Blood samples were collected to determine the Ctrough_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Pre-dose at Week 12.
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. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	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. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

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