Non-Small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease
Interventions
BIOLOGICALIpilimumab
Specified dose on specified day
BIOLOGICALNivolumab
Specified dose on specified day
DRUGCarboplatin
Specified dose on specified day
DRUGPaclitaxel
Specified dose on specified day
DRUGPemetrexed
Specified dose on specified day
DRUGCisplatin
Specified dose on specified day
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Participants with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 * Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria * Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period
Exclusion criteria
* Participants with known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded * Participants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excluded * Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment Other protocol inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of randomization to date of death (assessed up to October 2019, approximately 23 months) | OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by BICR | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression. |
| Duration of Response (DoR) | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only. |
| Time to Response (TTR) | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only. |
| Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | ORR was defined as the proportion of randomized participants with a best overall response (BOR) of confirmed complete or partial response per BICR using RECIST v1.1. BOR was assessed from randomization until documented progression, start of palliative local or subsequent anti-cancer therapy-whichever came first. If none occurred, all response data contributed to BOR. For those treated beyond progression, BOR was based on responses before initial RECIST-defined progression. PD-L1 expression was measured via Dako PD-L1 IHC 28-8 pharmDx test as the percentage of tumor cells with membrane staining among ≥100 evaluable cells. Expression was categorized as ≥1%, \<1%, not quantifiable, ≥50%, or 1-49%. |
| Progression Free Survival (PFS) by BICR | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. |
| OS by PD-L1 Tumor Cell Expression | From date of randomization to date of death (assessed up to October 2024, approximately 72 months) | OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. |
| PFS by BICR by Tumor Mutational Burden | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. |
| ORR by BICR by Tumor Mutational Burden | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression. |
| OS by Tumor Mutational Burden | From date of randomization to date of death (assessed up to October 2024, approximately 72 months) | OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. |
| PFS by BICR by PD-L1 Tumor Cell Expression | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months) | PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, France, Germany, Ireland, Italy, Japan, Mexico, Poland, Romania, Russia, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
707 Randomized and treated
Participants by arm
| Arm | Count |
|---|---|
| Treatment A Nivolumab + Ipilimumab + Chemotherapy | 361 |
| Treatment B Chemotherapy only | 358 |
| Total | 719 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Adverse Event unrelated to study drug | 1 | 0 |
| Randomization | no longer meets study criteria | 1 | 4 |
| Randomization | other reasons | 0 | 2 |
| Randomization | participant withdrew consent | 1 | 3 |
| Treatment Period | Administrative reason by sponsor | 0 | 2 |
| Treatment Period | Adverse event unrelated to study drug | 31 | 27 |
| Treatment Period | Death | 7 | 1 |
| Treatment Period | Disease Progression | 184 | 174 |
| Treatment Period | Lost to Follow-up | 0 | 1 |
| Treatment Period | Not reported | 1 | 0 |
| Treatment Period | other reasons | 10 | 5 |
| Treatment Period | Participant withdrew consent | 4 | 5 |
| Treatment Period | Request to D/C treatment | 2 | 10 |
| Treatment Period | Study Drug Toxicity | 70 | 24 |
Baseline characteristics
| Characteristic | Treatment A | Treatment B | Total |
|---|---|---|---|
| Age, Continuous | 65.0 Years STANDARD_DEVIATION 8.3 | 65.0 Years STANDARD_DEVIATION 10.3 | 65.0 Years STANDARD_DEVIATION 9.4 |
| Age, Customized ≥65 and ˂75 years old | 148 Count of Participants | 147 Count of Participants | 41.0 Count of Participants |
| Age, Customized ˂65 years old | 176 Count of Participants | 178 Count of Participants | 49.2 Count of Participants |
| Age, Customized ≥75 years old | 37 Count of Participants | 33 Count of Participants | 9.7 Count of Participants |
| Age, Customized ≥85 years old | 0 Count of Participants | 2 Count of Participants | 0.3 Count of Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 31 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 154 Participants | 158 Participants | 312 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 178 Participants | 169 Participants | 347 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 30 Participants | 60 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 11 Participants |
| Race (NIH/OMB) White | 322 Participants | 316 Participants | 638 Participants |
| Sex: Female, Male Female | 109 Participants | 106 Participants | 215 Participants |
| Sex: Female, Male Male | 252 Participants | 252 Participants | 504 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 304 / 361 | 318 / 358 |
| other Total, other adverse events | 343 / 358 | 329 / 349 |
| serious Total, serious adverse events | 259 / 358 | 197 / 349 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time frame: From date of randomization to date of death (assessed up to October 2019, approximately 23 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Overall Survival (OS) | 14.13 Months |
| Treatment B | Overall Survival (OS) | 10.74 Months |
p-value: 0.000695% CI: [0.56, 0.86]Log-rank test stratified
Secondary
Duration of Response (DoR)
DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All confirmed Responders, Global Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Duration of Response (DoR) | 13.01 Months |
| Treatment B | Duration of Response (DoR) | 5.59 Months |
Secondary
Objective Response Rate (ORR) by BICR
ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A | Objective Response Rate (ORR) by BICR | 38.0 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR | 25.1 Percentage of Participants |
95% CI: [6, 19.4]Mantel Haenszel
Secondary
Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression
ORR was defined as the proportion of randomized participants with a best overall response (BOR) of confirmed complete or partial response per BICR using RECIST v1.1. BOR was assessed from randomization until documented progression, start of palliative local or subsequent anti-cancer therapy-whichever came first. If none occurred, all response data contributed to BOR. For those treated beyond progression, BOR was based on responses before initial RECIST-defined progression. PD-L1 expression was measured via Dako PD-L1 IHC 28-8 pharmDx test as the percentage of tumor cells with membrane staining among ≥100 evaluable cells. Expression was categorized as ≥1%, \<1%, not quantifiable, ≥50%, or 1-49%.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION < 1% | 31.1 Percentage of Participants |
| Treatment A | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION 1 - 49% | 38.3 Percentage of Participants |
| Treatment A | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 36.4 Percentage of Participants |
| Treatment A | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION >= 50% | 50.0 Percentage of Participants |
| Treatment A | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION ≥1% | 42.6 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION >= 50% | 31.6 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION ≥1% | 27.5 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION < 1% | 20.2 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 32.0 Percentage of Participants |
| Treatment B | Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | BASELINE PD-L1 EXPRESSION 1 - 49% | 23.6 Percentage of Participants |
Secondary
ORR by BICR by Tumor Mutational Burden
ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population with tumor mutational burden measurements
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | ORR by BICR by Tumor Mutational Burden | ≥ 10 Mutations/MB | 45.5 Percentage of Participants |
| Treatment A | ORR by BICR by Tumor Mutational Burden | < 10 Mutations/MB | 31.6 Percentage of Participants |
| Treatment A | ORR by BICR by Tumor Mutational Burden | Overall | 37.6 Percentage of Participants |
| Treatment A | ORR by BICR by Tumor Mutational Burden | Not Evaluable | 36.4 Percentage of Participants |
| Treatment B | ORR by BICR by Tumor Mutational Burden | Not Evaluable | 21.2 Percentage of Participants |
| Treatment B | ORR by BICR by Tumor Mutational Burden | ≥ 10 Mutations/MB | 29.3 Percentage of Participants |
| Treatment B | ORR by BICR by Tumor Mutational Burden | Overall | 27.9 Percentage of Participants |
| Treatment B | ORR by BICR by Tumor Mutational Burden | < 10 Mutations/MB | 27.0 Percentage of Participants |
Secondary
OS by PD-L1 Tumor Cell Expression
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time frame: From date of randomization to date of death (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population with PD-L1 measurements
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A | OS by PD-L1 Tumor Cell Expression | >= 1% PD-L1 Expression | 15.80 Months |
| Treatment A | OS by PD-L1 Tumor Cell Expression | with >= 50% PD-L1 Expression | 18.91 Months |
| Treatment A | OS by PD-L1 Tumor Cell Expression | with 1-49% PD-L1 Expression | 15.20 Months |
| Treatment A | OS by PD-L1 Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 10.84 Months |
| Treatment A | OS by PD-L1 Tumor Cell Expression | < 1% PD-L1 Expression | 17.74 Months |
| Treatment B | OS by PD-L1 Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 17.05 Months |
| Treatment B | OS by PD-L1 Tumor Cell Expression | < 1% PD-L1 Expression | 9.79 Months |
| Treatment B | OS by PD-L1 Tumor Cell Expression | >= 1% PD-L1 Expression | 10.89 Months |
| Treatment B | OS by PD-L1 Tumor Cell Expression | with 1-49% PD-L1 Expression | 10.37 Months |
| Treatment B | OS by PD-L1 Tumor Cell Expression | with >= 50% PD-L1 Expression | 12.93 Months |
Secondary
OS by Tumor Mutational Burden
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time frame: From date of randomization to date of death (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population with tumor mutational burden measurements
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A | OS by Tumor Mutational Burden | ≥ 10 Mutations/MB | 15.05 Months |
| Treatment A | OS by Tumor Mutational Burden | < 10 Mutations/MB | 16.51 Months |
| Treatment A | OS by Tumor Mutational Burden | Overall | 15.57 Months |
| Treatment A | OS by Tumor Mutational Burden | Not Evaluable | 17.10 Months |
| Treatment B | OS by Tumor Mutational Burden | Not Evaluable | 9.46 Months |
| Treatment B | OS by Tumor Mutational Burden | ≥ 10 Mutations/MB | 10.76 Months |
| Treatment B | OS by Tumor Mutational Burden | Overall | 12.06 Months |
| Treatment B | OS by Tumor Mutational Burden | < 10 Mutations/MB | 12.55 Months |
Secondary
PFS by BICR by PD-L1 Tumor Cell Expression
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A | PFS by BICR by PD-L1 Tumor Cell Expression | >= 1% PD-L1 Expression | 6.87 Months |
| Treatment A | PFS by BICR by PD-L1 Tumor Cell Expression | with >= 50% PD-L1 Expression | 8.28 Months |
| Treatment A | PFS by BICR by PD-L1 Tumor Cell Expression | with 1-49% PD-L1 Expression | 6.74 Months |
| Treatment A | PFS by BICR by PD-L1 Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 6.95 Months |
| Treatment A | PFS by BICR by PD-L1 Tumor Cell Expression | < 1% PD-L1 Expression | 5.78 Months |
| Treatment B | PFS by BICR by PD-L1 Tumor Cell Expression | Non-Quantifiable PD-L1 Expression | 6.77 Months |
| Treatment B | PFS by BICR by PD-L1 Tumor Cell Expression | < 1% PD-L1 Expression | 4.96 Months |
| Treatment B | PFS by BICR by PD-L1 Tumor Cell Expression | >= 1% PD-L1 Expression | 4.70 Months |
| Treatment B | PFS by BICR by PD-L1 Tumor Cell Expression | with 1-49% PD-L1 Expression | 5.29 Months |
| Treatment B | PFS by BICR by PD-L1 Tumor Cell Expression | with >= 50% PD-L1 Expression | 4.53 Months |
Secondary
PFS by BICR by Tumor Mutational Burden
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population with tumor mutational burden measurements
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A | PFS by BICR by Tumor Mutational Burden | ≥ 10 Mutations/MB | 8.94 Months |
| Treatment A | PFS by BICR by Tumor Mutational Burden | < 10 Mutations/MB | 5.62 Months |
| Treatment A | PFS by BICR by Tumor Mutational Burden | Overall | 6.37 Months |
| Treatment A | PFS by BICR by Tumor Mutational Burden | Not Evaluable | 6.74 Months |
| Treatment B | PFS by BICR by Tumor Mutational Burden | Not Evaluable | 5.45 Months |
| Treatment B | PFS by BICR by Tumor Mutational Burden | ≥ 10 Mutations/MB | 4.70 Months |
| Treatment B | PFS by BICR by Tumor Mutational Burden | Overall | 4.96 Months |
| Treatment B | PFS by BICR by Tumor Mutational Burden | < 10 Mutations/MB | 5.16 Months |
Secondary
Progression Free Survival (PFS) by BICR
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Progression Free Survival (PFS) by BICR | 6.74 Months |
| Treatment B | Progression Free Survival (PFS) by BICR | 5.26 Months |
95% CI: [0.59, 0.82]Log-rank test stratified
Secondary
Time to Response (TTR)
TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only.
Time frame: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
Population: All Confirmed Responders, Global Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Response (TTR) | 2.53 Months |
| Treatment B | Time to Response (TTR) | 1.58 Months |
Post Hoc
Overall Survival (OS)
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time frame: From date of randomization to date of death (assessed up to October 2024, approximately 72 months)
Population: All Randomized Participants, Global Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Overall Survival (OS) | 15.80 Months |
| Treatment B | Overall Survival (OS) | 10.96 Months |
95% CI: [0.63, 0.87]Stratified Cox proportional hazard model