Non - Small Cell Lung Cancer NSCLC
Conditions
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.
Interventions
DRUGGemcitabine
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.
MEDI4736 (durvalumab) treatment by intravenous infusion
DRUGVinorelbine
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.
DRUGErlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
DRUGMEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
DRUGtremelimumab (anti-CTLA4)
tremelimumab (anti-CTLA4) treatment by intravenous infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization (Day 1) until death due to any cause, approximately 36 months | The OS was defined as the time from the date of randomization until death due to any cause. |
| Progression-Free Survival (PFS) | 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. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS, Contribution of the Components Analysis of Sub-study B | 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. | 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 |
| Objective Response Rate (ORR) | 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. | 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. |
| Duration of Response (DoR) | 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. | 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 |
| OS, Contribution of the Components Analysis of Sub-study B | From randomization (Day 1) until death due to any cause, approximately 36 months | The OS was defined as the time from the date of randomization until death due to any cause. |
| Percentage of Participants Alive and Progression Free at 12 Months (APF12) | Tumour scans performed at baseline then every ~8 weeks up to 12 months. | 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 |
| Time From Randomisation to Second Progression (PFS2) of Sub-study B | 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. | 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. |
| Percentage of Participants Alive and Progression Free at 6 Months (APF6) | Tumour scans performed at baseline then every ~8 weeks up to 6 months | 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 |
| Percentage of Participants Alive at 12 Months (OS12) | From randomization (Day 1) up to 12 months | 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. |
Countries
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, United States
Participant flow
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).
Pre-assignment details
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 \[PD-L1 low/neg (\<25% of TC expressing PD-L1)\].
Participants by arm
| Arm | Count |
|---|---|
| Sub-study A: Durvalumab Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses). | 62 |
| 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. | 64 |
| 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). | 174 |
| 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. | 118 |
| Sub-study B: Durvalumab Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses). | 117 |
| 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). | 60 |
| Total | 595 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 47 | 48 | 114 | 74 | 77 | 44 |
| Overall Study | Eligibility criteria not fulfilled | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 | 1 | 2 | 1 |
| Overall Study | Other | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 10 | 11 | 23 | 9 | 4 |
Baseline characteristics
| Characteristic | Sub-study A: Durvalumab | Sub-study A: SoC | Sub-study B: Durvalumab+Tremelimumab | Sub-study B: SoC | Sub-study B: Durvalumab | Sub-study B: Tremelimumab | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized >=50 to <65 years | 31 Participants | 25 Participants | 79 Participants | 49 Participants | 52 Participants | 27 Participants | 263 Participants |
| Age, Customized <50 years | 3 Participants | 11 Participants | 16 Participants | 8 Participants | 13 Participants | 4 Participants | 55 Participants |
| Age, Customized >=65 to <75 years | 24 Participants | 21 Participants | 64 Participants | 50 Participants | 39 Participants | 24 Participants | 222 Participants |
| Age, Customized >=75 years | 4 Participants | 7 Participants | 15 Participants | 11 Participants | 13 Participants | 5 Participants | 55 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 22 Participants | 23 Participants | 41 Participants | 41 Participants | 34 Participants | 16 Participants | 177 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 40 Participants | 129 Participants | 74 Participants | 79 Participants | 43 Participants | 405 Participants |
| Sex: Female, Male Female | 20 Participants | 16 Participants | 59 Participants | 37 Participants | 44 Participants | 21 Participants | 197 Participants |
| Sex: Female, Male Male | 42 Participants | 48 Participants | 115 Participants | 81 Participants | 73 Participants | 39 Participants | 398 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 48 / 62 | 55 / 64 | 118 / 174 | 90 / 118 | 83 / 117 | 46 / 60 |
| other Total, other adverse events | 52 / 62 | 59 / 63 | 139 / 173 | 100 / 110 | 99 / 117 | 48 / 60 |
| serious Total, serious adverse events | 23 / 62 | 16 / 63 | 65 / 173 | 28 / 110 | 36 / 117 | 23 / 60 |
Outcome results
Primary
Overall Survival (OS)
The OS was defined as the time from the date of randomization until death due to any cause.
Time frame: From randomization (Day 1) until death due to any cause, approximately 36 months
Population: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | Overall Survival (OS) | 11.7 months |
| Sub-study A: SoC | Overall Survival (OS) | 6.8 months |
| Sub-study B: Durvalumab+Tremelimumab | Overall Survival (OS) | 11.5 months |
| Sub-study B: SoC | Overall Survival (OS) | 8.7 months |
Comparison: For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.95% CI: [0.42, 0.93]
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.p-value: 0.10995% CI: [0.61, 1.05]Log Rank
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
Time frame: 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.
Population: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | Progression-Free Survival (PFS) | 3.8 months |
| Sub-study A: SoC | Progression-Free Survival (PFS) | 2.2 months |
| Sub-study B: Durvalumab+Tremelimumab | Progression-Free Survival (PFS) | 3.5 months |
| Sub-study B: SoC | Progression-Free Survival (PFS) | 3.5 months |
Comparison: For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.95% CI: [0.49, 1.04]
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.p-value: 0.05695% CI: [0.59, 1.01]Log Rank
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
Time frame: 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.
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | Duration of Response (DoR) | 9.5 months |
| Sub-study A: SoC | Duration of Response (DoR) | 4.8 months |
| Sub-study B: Durvalumab+Tremelimumab | Duration of Response (DoR) | 12.2 months |
| Sub-study B: SoC | Duration of Response (DoR) | 10.8 months |
| Sub-study B: Durvalumab | Duration of Response (DoR) | 10.0 months |
| Sub-study B: Tremelimumab | Duration of Response (DoR) | 4.7 months |
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.
Time frame: 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.
Population: Sub-study A and B: FAS included all randomized participants with measureable disease at baseline analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sub-study A: Durvalumab | Objective Response Rate (ORR) | 35.5 percentage of participants |
| Sub-study A: SoC | Objective Response Rate (ORR) | 12.5 percentage of participants |
| Sub-study B: Durvalumab+Tremelimumab | Objective Response Rate (ORR) | 14.9 percentage of participants |
| Sub-study B: SoC | Objective Response Rate (ORR) | 6.8 percentage of participants |
| Sub-study B: Durvalumab | Objective Response Rate (ORR) | 15.4 percentage of participants |
| Sub-study B: Tremelimumab | Objective Response Rate (ORR) | 6.7 percentage of participants |
Comparison: For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.95% CI: [1.61, 10.1]
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.p-value: 0.03795% CI: [1.1, 5.94]Regression, Logistic
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.p-value: 0.92395% CI: [0.51, 1.89]Regression, Logistic
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.p-value: 0.10995% CI: [0.91, 8.61]Regression, Logistic
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.
Time frame: From randomization (Day 1) until death due to any cause, approximately 36 months
Population: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | OS, Contribution of the Components Analysis of Sub-study B | 11.5 months |
| Sub-study A: SoC | OS, Contribution of the Components Analysis of Sub-study B | 10.0 months |
| Sub-study B: Durvalumab+Tremelimumab | OS, Contribution of the Components Analysis of Sub-study B | 6.9 months |
Comparison: As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.p-value: 0.88595% CI: [0.74, 1.3]Log Rank
Comparison: As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.p-value: 0.15395% CI: [0.56, 1.11]Log Rank
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
Time frame: Tumour scans performed at baseline then every ~8 weeks up to 12 months.
Population: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sub-study A: Durvalumab | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 19.4 percentage of participants |
| Sub-study A: SoC | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 9.9 percentage of participants |
| Sub-study B: Durvalumab+Tremelimumab | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 20.6 percentage of participants |
| Sub-study B: SoC | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 8.0 percentage of participants |
| Sub-study B: Durvalumab | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 15.0 percentage of participants |
| Sub-study B: Tremelimumab | Percentage of Participants Alive and Progression Free at 12 Months (APF12) | 7.3 percentage of participants |
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
Time frame: Tumour scans performed at baseline then every ~8 weeks up to 6 months
Population: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sub-study A: Durvalumab | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 35.5 percentage of participants |
| Sub-study A: SoC | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 24.1 percentage of participants |
| Sub-study B: Durvalumab+Tremelimumab | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 31.5 percentage of participants |
| Sub-study B: SoC | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 27.6 percentage of participants |
| Sub-study B: Durvalumab | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 27.2 percentage of participants |
| Sub-study B: Tremelimumab | Percentage of Participants Alive and Progression Free at 6 Months (APF6) | 14.5 percentage of participants |
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.
Time frame: From randomization (Day 1) up to 12 months
Population: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sub-study A: Durvalumab | Percentage of Participants Alive at 12 Months (OS12) | 49.3 percentage of participants |
| Sub-study A: SoC | Percentage of Participants Alive at 12 Months (OS12) | 31.3 percentage of participants |
| Sub-study B: Durvalumab+Tremelimumab | Percentage of Participants Alive at 12 Months (OS12) | 49.5 percentage of participants |
| Sub-study B: SoC | Percentage of Participants Alive at 12 Months (OS12) | 38.8 percentage of participants |
| Sub-study B: Durvalumab | Percentage of Participants Alive at 12 Months (OS12) | 43.6 percentage of participants |
| Sub-study B: Tremelimumab | Percentage of Participants Alive at 12 Months (OS12) | 41.2 percentage of participants |
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.p-value: 0.063z-test
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
Time frame: 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.
Population: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | PFS, Contribution of the Components Analysis of Sub-study B | 3.5 months |
| Sub-study A: SoC | PFS, Contribution of the Components Analysis of Sub-study B | 3.1 months |
| Sub-study B: Durvalumab+Tremelimumab | PFS, Contribution of the Components Analysis of Sub-study B | 2.1 months |
Comparison: As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.p-value: 0.28295% CI: [0.68, 1.12]Log Rank
Comparison: As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.p-value: 0.01195% CI: [0.49, 0.92]Log Rank
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.
Time frame: 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.
Population: FAS included all randomized participants analyzed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sub-study A: Durvalumab | Time From Randomisation to Second Progression (PFS2) of Sub-study B | 9.1 months |
| Sub-study A: SoC | Time From Randomisation to Second Progression (PFS2) of Sub-study B | 6.7 months |
| Sub-study B: Durvalumab+Tremelimumab | Time From Randomisation to Second Progression (PFS2) of Sub-study B | 8.0 months |
| Sub-study B: SoC | Time From Randomisation to Second Progression (PFS2) of Sub-study B | 5.7 months |
Comparison: For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.p-value: 0.00295% CI: [0.49, 0.85]Log Rank