Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
programmed cell death ligand 1 (PD-L1), MEDI4736, Cytotoxic T-lymphocyte-associated antigen 4 {CTLA-4}, PFS, SCCHN
Brief summary
This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease.
Detailed description
Patients will be randomized in a 2:1:1 ratio to MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or SoC. Patients in all arms will continue therapy until progression. Tumor assessments will be performed on computed tomography scans or magnetic resonance imaging scans, preferably with intravenous (IV) contrast. Efficacy for all patients will be assessed by objective tumor assessments every 6 weeks for the first 24 weeks, then every 8 weeks thereafter until treatment discontinuation due to progression or toxicity. All patients will be followed every 3 months for survival after progression is confirmed.
Interventions
BIOLOGICALMEDI4736
Anti-PD-L1 antibody
BIOLOGICALTremelimumab
Anti-CTLA-4 Antibody
BIOLOGICALMEDI4736+Tremelimumab
BIOLOGICALCetuximab
Monoclonal Antibody
Chemotherapy Agent
DRUGCisplatin
Chemotherapy agent
DRUGCarboplatin
Chemotherapy Agent
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
1. Age ≥18 years at the time of screening 2. Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx). 3. A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy. 4. No prior systemic chemotherapy for recurrent or metastatic disease 5. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment 6. No prior exposure to immune-mediated therapy,
Exclusion criteria
1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland) 2. Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting 3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment 4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis, Crohn's disease\], diverticulitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | From date of randomization until time of final analysis, an average of approximately 4 years | Number of participants with Overall Survival (OS) |
| Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup | From date of randomization until time of final analysis, an average of approximately 4 years | Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: \>= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR) |
| Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression |
| Overall Survival (OS) Status in the All-comers (Full Analysis Set) | From date of randomization until time of final analysis, an average of approximately 4 years | Number of participants with Overall Survival (OS) |
| Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) | From date of randomization until time of final analysis, an average of approximately 4 years | Number of participants with Overall Survival (OS) |
| Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | 12, 18 and 24 months after randomization | Percentage of patients alive |
| Progression Free Survival (PFS) in the All-comers (Full Analysis Set) | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: \>= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR) |
| Duration of Response (DoR) in the All-comers (Full Analysis Set) | Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years | Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression |
| Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) | From date of randomization until time of final analysis, an average of approximately 4 years | Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) |
| Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | 12, 18 and 24 months after randomization | Percentage of patients alive |
Countries
Austria, Belgium, Brazil, Canada, France, Germany, Greece, India, Italy, Japan, Philippines, Poland, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
Patients meeting all the eligibility criteria were randomized 2:1:1 to durvalumab plus tremelimumab combination therapy, durvalumab monotherapy or standard of care.
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab + Tremelimumab tremelimumab (75 mg) via IV infusion every 4 weeks for a maximum of 4 doses, and durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | 413 |
| Durvalumab durvalumab (1500 mg) via IV infusion every 4 weeks until disease progression | 204 |
| Standard of Care (SOC) either cisplatin (at a dose of 100 mg/m2 of body surface area as an IV infusion) or carboplatin (at an area under the concentration curve of 5 mg/mL/min as an IV infusion) on Day 1 of up to six 3-week cycles, and an infusion of 5-fluorouracil (5FU) (at a dose of 1000 mg/m2/day on Days 1 through 4) every 3 weeks, along with 400 mg/m2 of cetuximab on Cycle 1 Day 1 and 250 mg/m2 weekly for up to 6 cycles and maintenance cetuximab at 250 mg/m2 administered via IV infusion weekly thereafter in patients who achieved stable disease (SD) or better upon completion of chemotherapy until disease progression, toxicity, or withdrawal of consent | 206 |
| Total | 823 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 352 | 174 | 161 |
| Overall Study | Patients alive or lost to follow-up at DCO | 53 | 25 | 29 |
| Overall Study | Withdrawal by Subject | 8 | 5 | 16 |
Baseline characteristics
| Characteristic | Durvalumab + Tremelimumab | Durvalumab | Standard of Care (SOC) | Total |
|---|---|---|---|---|
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 9.56 | 60.2 Years STANDARD_DEVIATION 10.41 | 60.9 Years STANDARD_DEVIATION 9.45 | 60.5 Years STANDARD_DEVIATION 9.74 |
| Race/Ethnicity, Customized Asian | 109 Participants | 54 Participants | 42 Participants | 205 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 3 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 298 Participants | 145 Participants | 160 Participants | 603 Participants |
| Sex: Female, Male Female | 73 Participants | 29 Participants | 32 Participants | 134 Participants |
| Sex: Female, Male Male | 340 Participants | 175 Participants | 174 Participants | 689 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 356 / 413 | 176 / 204 | 171 / 206 |
| other Total, other adverse events | 317 / 408 | 153 / 202 | 182 / 196 |
| serious Total, serious adverse events | 168 / 408 | 78 / 202 | 94 / 196 |
Outcome results
Primary
Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup | 11.2 Months |
| Durvalumab | Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup | 10.9 Months |
| Standard of Care (SOC) | Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup | 10.9 Months |
Primary
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC)
Number of participants with Overall Survival (OS)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Voluntary Discontinuation by subject | 1 Participants |
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Death | 162 Participants |
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Alive or lost to follow up | 27 Participants |
| Durvalumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Voluntary Discontinuation by subject | 1 Participants |
| Durvalumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Death | 84 Participants |
| Durvalumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Alive or lost to follow up | 14 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Death | 77 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Alive or lost to follow up | 14 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab Versus Standard of Care (SOC) | Voluntary Discontinuation by subject | 3 Participants |
Comparison: Statistical analysis of number of deathsp-value: 0.78795% CI: [0.69, 1.32]Log Rank
Secondary
Duration of Response (DoR) in the All-comers (Full Analysis Set)
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: All-comers (Full analysis set)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Duration of Response (DoR) in the All-comers (Full Analysis Set) | 9.2 Months |
| Durvalumab | Duration of Response (DoR) in the All-comers (Full Analysis Set) | 11.9 Months |
| Standard of Care (SOC) | Duration of Response (DoR) in the All-comers (Full Analysis Set) | 4.2 Months |
Secondary
Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup
Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup | 6.5 Months |
| Durvalumab | Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup | 12.3 Months |
| Standard of Care (SOC) | Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup | 4.2 Months |
Secondary
Objective Response Rate (ORR) in the All-comers (Full Analysis Set)
Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: \>= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: All-comers (Full analysis set)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | Response | 90 Participants |
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | No response | 323 Participants |
| Durvalumab | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | Response | 35 Participants |
| Durvalumab | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | No response | 169 Participants |
| Standard of Care (SOC) | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | Response | 101 Participants |
| Standard of Care (SOC) | Objective Response Rate (ORR) in the All-comers (Full Analysis Set) | No response | 105 Participants |
p-value: <0.00195% CI: [0.13, 0.33]Regression, Logistic
p-value: <0.00195% CI: [0.2, 0.41]Regression, Logistic
Secondary
Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup
Number (%) of patients with at least 1 visit response of complete response (CR) or partial response (PR). Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions (TL) and assessed by MRI or CT: CR: Disappearance of all TLs since baseline; PR: \>= 30% decrease in the sum of diameters of TLs; Overall Response (OR = CR + PR)
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | Response | 48 Participants |
| Durvalumab + Tremelimumab | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | No response | 142 Participants |
| Durvalumab | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | Response | 16 Participants |
| Durvalumab | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | No response | 83 Participants |
| Standard of Care (SOC) | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | Response | 47 Participants |
| Standard of Care (SOC) | Objective Response Rate (ORR) in the PD-L1 TC/IC High Subgroup | No response | 47 Participants |
Comparison: Statistical analysis of number with a responsep-value: <0.00195% CI: [0.1, 0.37]Regression, Logistic
Comparison: Statistical analysis of number with a responsep-value: <0.00195% CI: [0.2, 0.57]Regression, Logistic
Secondary
Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)
Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Population: All-comers (Full analysis set)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) | 10.7 Months |
| Durvalumab | Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) | 9.9 Months |
| Standard of Care (SOC) | Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set) | 10.3 Months |
Secondary
Overall Survival (OS) Status in the All-comers (Full Analysis Set)
Number of participants with Overall Survival (OS)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Population: All-comers (Full analysis set)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Voluntary Discontinuation by subject | 4 Participants |
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Death | 356 Participants |
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Alive or lost to follow up | 53 Participants |
| Durvalumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Voluntary Discontinuation by subject | 3 Participants |
| Durvalumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Death | 176 Participants |
| Durvalumab | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Alive or lost to follow up | 25 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Death | 171 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Alive or lost to follow up | 29 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the All-comers (Full Analysis Set) | Voluntary Discontinuation by subject | 6 Participants |
Comparison: Statistical analysis of number of deathsp-value: 0.81195% CI: [0.83, 1.27]Log Rank
Comparison: Statistical analysis of number of deathsp-value: 0.62495% CI: [0.87, 1.25]Log Rank
Secondary
Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)
Number of participants with Overall Survival (OS)
Time frame: From date of randomization until time of final analysis, an average of approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Durvalumab + Tremelimumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) | 162 Participants |
| Durvalumab | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) | 84 Participants |
| Standard of Care (SOC) | Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC) | 77 Participants |
p-value: 0.63495% CI: [0.8, 1.39]Log Rank
Secondary
Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)
Percentage of patients alive
Time frame: 12, 18 and 24 months after randomization
Population: All-comers (Full analysis set)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 18 months | 30.7 % of participants |
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 12 months | 46.5 % of participants |
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 24 months | 22.9 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 18 months | 31.2 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 12 months | 42.8 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 24 months | 24.7 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 12 months | 43.8 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 24 months | 23.2 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set) | at 18 months | 29.7 % of participants |
Secondary
Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup
Percentage of patients alive
Time frame: 12, 18 and 24 months after randomization
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 18 months | 31.8 % of participants |
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 12 months | 49.3 % of participants |
| Durvalumab + Tremelimumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 24 months | 23.9 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 18 months | 34.7 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 12 months | 48.0 % of participants |
| Durvalumab | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 24 months | 27.6 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 12 months | 44.0 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 24 months | 26.4 % of participants |
| Standard of Care (SOC) | Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup | at 18 months | 30.8 % of participants |
Secondary
Progression Free Survival (PFS) in the All-comers (Full Analysis Set)
Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: All-comers (Full analysis set)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Progression Free Survival (PFS) in the All-comers (Full Analysis Set) | 2.8 Months |
| Durvalumab | Progression Free Survival (PFS) in the All-comers (Full Analysis Set) | 2.8 Months |
| Standard of Care (SOC) | Progression Free Survival (PFS) in the All-comers (Full Analysis Set) | 5.4 Months |
p-value: 0.00695% CI: [1.1, 1.68]Log Rank
p-value: 0.00895% CI: [1.06, 1.53]Log Rank
Secondary
Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup
Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years
Population: PD-L1 TC/IC subgroup
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab + Tremelimumab | Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup | 2.8 Months |
| Durvalumab | Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup | 2.8 Months |
| Standard of Care (SOC) | Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup | 5.3 Months |
p-value: 0.28795% CI: [0.94, 1.8]Log Rank
p-value: 0.02895% CI: [0.99, 1.76]Log Rank