A Global Study to Assess the Effects of MEDI4736 (Durvalu... | NCT02352948 | Trialant
NCT02352948
Sponsor
AstraZeneca
Status
Completed
Last Update Posted
Jul 26, 2024Actual
Enrollment
597Actual
Phase
Phase 3
Conditions
Non - Small Cell Lung Cancer NSCLC
Interventions
MEDI4736 (durvalumab)
Vinorelbine
Gemcitabine
Erlotinib
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
tremelimumab (anti-CTLA4)
Countries
United States
Australia
Belgium
Bulgaria
Canada
Chile
Czechia
France
Germany
Greece
Hong Kong
Hungary
Israel
Italy
Japan
Netherlands
Poland
Romania
Russia
Serbia
Singapore
South Korea
Spain
Taiwan
Thailand
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02352948
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
D4191C00004
Secondary IDs
ID
Type
Description
Link
2014-000338-46
EudraCT Number
Brief Title
A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Official Title
A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).
Acronym
ARCTIC
Organization
AstraZenecaINDUSTRY
Status Module
Record Verification Date
Jul 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 13, 2015Actual
Primary Completion Date
Feb 9, 2018Actual
Completion Date
Aug 30, 2023Actual
First Submitted Date
Jan 28, 2015
First Submission Date that Met QC Criteria
Jan 28, 2015
First Posted Date
Feb 2, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 7, 2019
Results First Submitted that Met QC Criteria
Mar 25, 2019
Results First Posted Date
Apr 16, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jul 25, 2024
Last Update Posted Date
Jul 26, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AstraZenecaINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the treatment of male and female patients with locally advanced or metastatic NSCLC (Stage IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1 platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements are not eligible for the study (prospective testing is not planned within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor (erlotinib [TARCEVA®]), gemcitabine or vinorelbine (NAVELBINE®)
Detailed Description
The study has an umbrella design with 2 sub-studies: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 (durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of Care. The two substudies may have different durations of recruitment periods due to differences in patient population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occurring at different time points.
Conditions Module
Conditions
Non - Small Cell Lung Cancer NSCLC
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
597Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
MEDI4736 (durvalumab) monotherapy in Sub-study A
Experimental
MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
Drug: MEDI4736 (durvalumab)
Standard of Care in Sub-study A
Active Comparator
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
Drug: Vinorelbine
Drug: Gemcitabine
Drug: Erlotinib
MEDI4736 (durvalumab) + tremelimumab in Sub-study B
Experimental
MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
Standard of Care in Sub-study B
Active Comparator
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
Drug: Vinorelbine
Drug: Gemcitabine
Drug: Erlotinib
MEDI4736 (durvalumab) monotherapy in Sub-study B
Experimental
MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
MEDI4736 (durvalumab)
Drug
MEDI4736 (durvalumab) treatment by intravenous infusion
MEDI4736 (durvalumab) monotherapy in Sub-study A
MEDI4736 (durvalumab) monotherapy in Sub-study B
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Overall Survival (OS)
The OS was defined as the time from the date of randomization until death due to any cause.
From randomization (Day 1) until death due to any cause, approximately 36 months
Progression-Free Survival (PFS)
The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to response evaluation criteria in solid tumours (RECIST) version 1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary Outcomes
Measure
Description
Time Frame
OS, Contribution of the Components Analysis of Sub-study B
The OS was defined as the time from the date of randomization until death due to any cause.
From randomization (Day 1) until death due to any cause, approximately 36 months
Percentage of Participants Alive at 12 Months (OS12)
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Aged at least 18 years
Documented evidence of NSCLC (Stage IIIB/ IV disease)
Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
World Health Organization (WHO) Performance Status of 0 or 1
Estimated life expectancy more than 12 weeks
Exclusion Criteria:
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4
Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
Active or prior documented autoimmune disease within the past 2 years
Evidence of severe or uncontrolled systemic disease, including active bleeding diatheses or active infections including hepatitis B, C and HIV
Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2 from previous anti-cancer therapy
Known EGFR TK activating mutations or ALK rearrangements
Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.
Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. doi: 10.1016/j.annonc.2020.02.006. Epub 2020 Feb 20.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
The study had a pre-screening period to determine the programmed cell death ligand 1 (PD-L1) status, followed by a screening period and 12 month treatment period. A total of 595 participants were randomized to either sub-study A [PD-L1 high (>=25% of tumor cell (TC) expressing PD-L1)] or sub-study B [PD-L1 low/neg (<25% of TC expressing PD-L1)].
Recruitment Details
This study was divided into 2 parts, sub-study A (82 centers across Europe, Asia, and North America) and sub-study B (149 centers across Europe, Asia, North America, and South America) conducted between 13 January 2015 and 09 February 2018 (data cut-off date).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Sub-study A: Durvalumab
Participants received durvalumab (MEDI4736) 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (Q2W) for 12 months (up to 26 doses).
FG001
Sub-study A: Standard of Care (SoC)
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jan 8, 2018
Feb 7, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Argentina
Philippines
South Africa
Turkey (Türkiye)
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug: MEDI4736 (durvalumab)
tremelimumab in Sub-study B
Experimental
tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Drug: tremelimumab (anti-CTLA4)
Vinorelbine
Drug
Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.
Standard of Care in Sub-study A
Standard of Care in Sub-study B
Gemcitabine
Drug
Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.
Standard of Care in Sub-study A
Standard of Care in Sub-study B
Erlotinib
Drug
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
Standard of Care in Sub-study A
Standard of Care in Sub-study B
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
Drug
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
MEDI4736 (durvalumab) + tremelimumab in Sub-study B
tremelimumab (anti-CTLA4)
Drug
tremelimumab (anti-CTLA4) treatment by intravenous infusion
tremelimumab in Sub-study B
The OS12 was defined as the percentage of participants who were alive at 12 months after randomisation per Kaplan-Meier estimate of OS at 12 months.
From randomization (Day 1) up to 12 months
PFS, Contribution of the Components Analysis of Sub-study B
The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) among ITT participants who had measurable disease at baseline. CR was defined as disappearance of all target lesions (any pathological lymph nodes selected as target lesions 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 target lesions (taking as reference the baseline sum of diameters as long as criteria for PD are not met). The ORR was measured using Investigator assessments according to RECIST v1.1.
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Duration of Response (DoR)
The DoR 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. The DoR was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Percentage of Participants Alive and Progression Free at 6 Months (APF6)
The APF6 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 6 months after randomization per Kaplan-Meier estimate of PFS at 6 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Tumour scans performed at baseline then every ~8 weeks up to 6 months
Percentage of Participants Alive and Progression Free at 12 Months (APF12)
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Tumour scans performed at baseline then every ~8 weeks up to 12 months.
Time From Randomisation to Second Progression (PFS2) of Sub-study B
The PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the PFS endpoint or death and determined by local standard clinical practice and have included any of the following: objective radiological, symptomatic progression, or death. PFS2 was reported for sub-study B only.
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until first progression. Disease then assessed per local practice until 2nd progression. Assessed up to a maximum of approximately 3 years.
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/meter square (m^2) IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until progression of disease (PD), initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
FG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion every 4 weeks (Q4W) for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
FG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
FG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
FG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by every 12 weeks (Q12W) for 24 weeks (up to 9 doses).
FG00062 subjects
FG00164 subjects
FG002174 subjects
FG003118 subjects
FG004117 subjects
FG00560 subjects
Received Treatment
FG00062 subjects
FG00163 subjects
FG002173 subjects
FG003110 subjects
FG004117 subjects
FG00560 subjects
Completed Study Treatment
FG00015 subjects
FG0010 subjects
FG00236 subjects
FG0030 subjects
FG00423 subjects
FG0054 subjects
COMPLETED
Completed the Study
FG00013 subjects
FG0015 subjects
FG00245 subjects
FG00319 subjects
FG00429 subjects
FG00511 subjects
NOT COMPLETED
FG00049 subjects
FG00159 subjects
FG002129 subjects
FG00399 subjects
FG00488 subjects
FG00549 subjects
Type
Comment
Reasons
Death
FG00047 subjects
FG00148 subjects
FG002114 subjects
FG00374 subjects
FG00477 subjects
FG00544 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0031 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG00110 subjects
FG00211 subjects
FG00323 subjects
FG004
Eligibility criteria not fulfilled
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Other
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Sub-study A and B: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
BG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
BG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
BG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
BG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
BG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00062
BG00164
BG002174
BG003118
BG004117
BG00560
BG006595
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<50 years
BG0003
BG00111
BG00216
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00020
BG00116
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Overall Survival (OS)
The OS was defined as the time from the date of randomization until death due to any cause.
Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
Posted
Median
95% Confidence Interval
months
From randomization (Day 1) until death due to any cause, approximately 36 months
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003
Title
Denominators
Categories
Title
Measurements
OG00011.7(8.2 to 17.4)
OG0016.8(4.9 to 10.2)
OG00211.5(8.7 to 14.1)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.
Hazard Ratio (HR)
0.63
2-Sided
95
0.42
0.93
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Other
Sub-study A was not powered and thus no formal statistical comparisons were performed.
Primary
Progression-Free Survival (PFS)
The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to response evaluation criteria in solid tumours (RECIST) version 1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
Posted
Median
95% Confidence Interval
months
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Secondary
OS, Contribution of the Components Analysis of Sub-study B
The OS was defined as the time from the date of randomization until death due to any cause.
FAS included all randomized participants analyzed on an ITT basis.
Posted
Median
95% Confidence Interval
months
From randomization (Day 1) until death due to any cause, approximately 36 months
ID
Title
Description
OG000
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG001
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG002
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Secondary
Percentage of Participants Alive at 12 Months (OS12)
The OS12 was defined as the percentage of participants who were alive at 12 months after randomisation per Kaplan-Meier estimate of OS at 12 months.
Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
Posted
Number
95% Confidence Interval
percentage of participants
From randomization (Day 1) up to 12 months
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
Secondary
PFS, Contribution of the Components Analysis of Sub-study B
The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
FAS included all randomized participants analyzed on an ITT basis.
Posted
Median
95% Confidence Interval
months
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
ID
Title
Description
OG000
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG001
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
Secondary
Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) among ITT participants who had measurable disease at baseline. CR was defined as disappearance of all target lesions (any pathological lymph nodes selected as target lesions 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 target lesions (taking as reference the baseline sum of diameters as long as criteria for PD are not met). The ORR was measured using Investigator assessments according to RECIST v1.1.
Sub-study A and B: FAS included all randomized participants with measureable disease at baseline analyzed on an ITT basis.
Posted
Number
percentage of participants
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Secondary
Duration of Response (DoR)
The DoR 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. The DoR was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Sub-study A and B: FAS included all randomized participants with measureable disease at baseline analyzed on an ITT basis. Only participants with objective response were analyzed.
Posted
Median
Inter-Quartile Range
months
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Secondary
Percentage of Participants Alive and Progression Free at 6 Months (APF6)
The APF6 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 6 months after randomization per Kaplan-Meier estimate of PFS at 6 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
Posted
Number
95% Confidence Interval
percentage of participants
Tumour scans performed at baseline then every ~8 weeks up to 6 months
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG002
Sub-study B: Durvalumab+Tremelimumab
Secondary
Percentage of Participants Alive and Progression Free at 12 Months (APF12)
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
Posted
Number
95% Confidence Interval
percentage of participants
Tumour scans performed at baseline then every ~8 weeks up to 12 months.
ID
Title
Description
OG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG002
Sub-study B: Durvalumab+Tremelimumab
Secondary
Time From Randomisation to Second Progression (PFS2) of Sub-study B
The PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the PFS endpoint or death and determined by local standard clinical practice and have included any of the following: objective radiological, symptomatic progression, or death. PFS2 was reported for sub-study B only.
FAS included all randomized participants analyzed on an ITT basis.
Posted
Median
95% Confidence Interval
months
Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until first progression. Disease then assessed per local practice until 2nd progression. Assessed up to a maximum of approximately 3 years.
ID
Title
Description
OG000
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG001
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Time Frame
From signature of informed consent up to 90 days after the last dose of durvalumab and/or tremelimumab and 30 days after the last dose of SoC, approximately 15 months.
Description
Sub-study A and B: Safety analysis set included all participants who received at least 1 dose of randomized treatment. All-cause mortality is defined as death due to any cause (including disease progression) for the entire duration of the study.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Sub-study A: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
48
62
23
62
52
62
EG001
Sub-study A: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
55
64
16
63
59
63
EG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
118
174
65
173
139
173
EG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
90
118
28
110
100
110
EG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
83
117
36
117
99
117
EG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
46
60
23
60
48
60
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0012 events2 affected63 at risk
EG0020 events0 affected173 at risk
EG0031 events1 affected110 at risk
EG0041 events1 affected117 at risk
EG0050 events0 affected60 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0015 events5 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0022 events2 affected173 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pericarditis
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Glucocorticoid deficiency
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hypopituitarism
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Inappropriate antidiuretic hormone secretion
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Thyroiditis
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0024 events3 affected173 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0024 events3 affected173 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Gastrointestinal toxicity
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Ileus paralytic
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Subileus
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0023 events3 affected173 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Death
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Fatigue
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0021 events1 affected173 at risk
EG003
General physical health deterioration
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hyperthermia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Oedema peripheral
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Perforation
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Sudden cardiac death
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0022 events2 affected173 at risk
EG003
Autoimmune hepatitis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0023 events3 affected173 at risk
EG003
Cholangitis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Cholestasis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Drug-induced liver injury
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Cytokine release syndrome
Immune system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Bacterial sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Bronchitis viral
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Campylobacter gastroenteritis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Escherichia infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Infectious pleural effusion
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pneumocystis jirovecii pneumonia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0005 events4 affected62 at risk
EG0013 events3 affected63 at risk
EG0027 events7 affected173 at risk
EG003
Pulmonary sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Varicella zoster virus infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Fractured ischium
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Amylase increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0022 events1 affected173 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Transaminases increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Diabetes mellitus inadequate control
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0022 events2 affected173 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Cancer pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0021 events1 affected173 at risk
EG003
Colorectal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Vocal cord paralysis
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Bronchial obstruction
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0010 events0 affected63 at risk
EG0027 events7 affected173 at risk
EG003
Pneumothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected62 at risk
EG0011 events1 affected63 at risk
EG0022 events2 affected173 at risk
EG003
Pneumothorax spontaneous
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected62 at risk
EG0010 events0 affected63 at risk
EG0025 events5 affected173 at risk
EG003
Orthostatic hypotension
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0011 events1 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Lymphangiosis carcinomatosa
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Prostate cancer stage IV
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected62 at risk
EG0010 events0 affected63 at risk
EG0020 events0 affected173 at risk
EG003
Tumour necrosis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.109
Hazard Ratio (HR)
0.80
2-Sided
95
0.61
1.05
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
OG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
Title
Denominators
Categories
Title
Measurements
OG0003.8(1.9 to 5.6)
OG0012.2(1.9 to 3.7)
OG0023.5(2.3 to 4.6)
OG0033.5(1.9 to 3.9)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.
Hazard Ratio (HR)
0.71
2-Sided
95
0.49
1.04
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Other
Sub-study A was not powered and thus no formal statistical comparisons were performed.
OG002
OG003
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.056
Hazard Ratio (HR)
0.77
2-Sided
95
0.59
1.01
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
Participants
OG000174
OG001117
OG00260
Title
Denominators
Categories
Title
Measurements
OG00011.5(8.7 to 14.1)
OG00110.0(7.1 to 13.2)
OG0026.9(3.9 to 13.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.885
Hazard Ratio (HR)
0.98
2-Sided
95
0.74
1.30
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
OG000
OG002
As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.153
Hazard Ratio (HR)
0.78
2-Sided
95
0.56
1.11
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
OG004117
OG00560
Title
Denominators
Categories
Title
Measurements
OG00049.3(36.3 to 61.0)
OG00131.3(20.2 to 43.0)
OG00249.5(41.7 to 56.7)
OG00338.8(29.9 to 47.7)
OG00443.6(34.4 to 52.4)
OG00541.2(28.7 to 53.3)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG002
OG003
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.
z-test
The variance is estimated using the delta method and Greenwood's formula.
0.063
The z-test statistic is the ratio of log-transformed ratio of the cumulative hazards in the 2 treatment arms divided by square root of the variance.
Superiority
OG002
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG000174
OG001117
OG00260
Title
Denominators
Categories
Title
Measurements
OG0003.5(2.3 to 4.6)
OG0013.1(1.9 to 3.7)
OG0022.1(1.8 to 3.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.282
Hazard Ratio (HR)
0.87
2-Sided
95
0.68
1.12
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
OG000
OG002
As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.011
Hazard Ratio (HR)
0.67
2-Sided
95
0.49
0.92
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.
Superiority
OG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
OG004117
OG00560
Title
Denominators
Categories
Title
Measurements
OG00035.5
OG00112.5
OG00214.9
OG0036.8
OG00415.4
OG0056.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.
Odds Ratio (OR)
3.87
2-Sided
95
1.61
10.10
The analysis was performed using logistic regression adjusting for SoC therapy (gemcitabine/vinorelbine versus erlotinib) and histology (squamous versus all other histology types), with 95% CI calculated by profile likelihood.
Other
Sub-study A was not powered and thus no formal statistical comparisons were performed.
OG002
OG003
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.
Regression, Logistic
0.037
Odds Ratio (OR)
2.43
2-Sided
95
1.10
5.94
The analysis was performed using logistic regression adjusting for SoC therapy (gemcitabine/vinorelbine versus erlotinib) and histology (squamous versus all other histology types), with 95% CI calculated by profile likelihood.
Superiority
OG002
OG004
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.
Regression, Logistic
0.923
Odds Ratio (OR)
0.97
2-Sided
95
0.51
1.89
The analysis was performed using logistic regression adjusting for SoC therapy (gemcitabine/vinorelbine versus erlotinib) and histology (squamous versus all other histology types), with 95% CI calculated by profile likelihood.
Superiority
OG002
OG005
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.
Regression, Logistic
0.109
Odds Ratio (OR)
2.46
2-Sided
95
0.91
8.61
The analysis was performed using logistic regression adjusting for SoC therapy (gemcitabine/vinorelbine versus erlotinib) and histology (squamous versus all other histology types), with 95% CI calculated by profile likelihood.
Superiority
OG002
Sub-study B: Durvalumab+Tremelimumab
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
OG004117
OG00560
Title
Denominators
Categories
Title
Measurements
OG0009.5(3.0 to 17.8)
OG0014.8(1.9 to 7.6)
OG00212.2(6.5 to NA)The upper limit of the 75th percentile was not calculated as it was not reached.
OG00310.8(5.6 to 12.2)
OG00410.0(4.0 to NA)The upper limit of the 75th percentile was not calculated as it was not reached.
OG0054.7(2.9 to NA)The upper limit of the 75th percentile was not calculated as it was not reached.
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
OG004117
OG00560
Title
Denominators
Categories
Title
Measurements
OG00035.5(23.9 to 47.3)
OG00124.1(14.1 to 35.6)
OG00231.5(24.6 to 38.7)
OG00327.6(19.0 to 36.7)
OG00427.2(19.4 to 35.6)
OG00514.5(6.9 to 24.9)
Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).
OG003
Sub-study B: SoC
Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.
OG004
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG005
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG00062
OG00164
OG002174
OG003118
OG004117
OG00560
Title
Denominators
Categories
Title
Measurements
OG00019.4(10.7 to 30.0)
OG0019.9(3.8 to 19.3)
OG00220.6(14.7 to 27.1)
OG0038.0(3.4 to 15.2)
OG00415.0(9.1 to 22.3)
OG0057.3(2.4 to 16.0)
OG002
Sub-study B: Durvalumab
Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).
OG003
Sub-study B: Tremelimumab
Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).
Units
Counts
Participants
OG000174
OG001118
OG002117
OG00360
Title
Denominators
Categories
Title
Measurements
OG0009.1(6.6 to 12.3)
OG0016.7(4.7 to 8.9)
OG0028.0(6.3 to 10.0)
OG0035.7(3.2 to 10.0)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.
Log Rank
The P-value arises from a stratified log-rank test adjusting for SoC therapy and histology, with ties handled by the Breslow approach.
0.002
Hazard Ratio (HR)
0.65
2-Sided
95
0.49
0.85
Hazard ratio and CI are estimated from a stratified Cox proportional hazards model with Breslow method to control for ties, stratification factors SoC therapy, and histology in strata statement, and CI is calculated using profile likelihood approach.