Gastric Cancer, Cancer of the Stomach, Esophagogastric Junction
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of investigational drug relatlimab plus nivolumab in combination with chemotherapy in participants with unresectable, untreated, locally advanced or metastatic gastric or GEJ cancer.
Interventions
Relatlimab + Nivolumab specified dose on specified days
Specified dose on specified days
Oxaliplatin + capecitabine
Oxaliplatin + leucovorin + fluorouracil
Oxaliplatin + tegafur/gimeracil/oteracil potassium
Sponsors
Study design
Eligibility
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 * Histologically- or cytologically-confirmed diagnosis of unresectable and either locally advanced, or metastatic gastric cancer or GEJ adenocarcinoma * No prior treatment with systemic treatment (including HER 2 inhibitors) given as primary therapy for unresectable and either locally advanced, or metastatic GC or GEJ adenocarcinoma * Tumor tissue must be provided for biomarker analyses
Exclusion criteria
* Participants with HER2 positive status * Participants with known untreated central nervous system (CNS) metastases * Uncontrolled or significant cardiovascular disease Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants | Up to 25 months | The number of LAG-3 Positive (\>=1%) participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized LAG-3 positive (\>=1%) participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions |
| BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection | From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months) | The number of LAG-3 Positive (\>=1%) participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized LAG-3 positive (\>=1%) participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the date of randomization to the date of death due to any cause (Up to 63 months) | Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For those without documentation of death, OS will be censored on the last date the participant was known to be alive. |
| Progression-Free Survival (PFS) | From the date of randomization to the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months) | Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR) and Investigator is defined as the time between the date of randomization and the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. Participants who die without a reported prior progression (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose to 30 days post last dose (Up to 60 months) | Number of participants with any grade adverse events (AEs), serious adverse events (SAE), and adverse events leading to discontinuation using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v 5.0). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization, results in significant disability, is a birth defect, or is an important medical event. |
| Objective Response Rate (ORR) | From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months) | Objective response rate (ORR) based on Blinded Independent Central Review (BICR) and Investigator assessments is defined as the number of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. |
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | From first dose to 30 days post last dose (Up to 60 months) | Number of participants with laboratory abnormalities in specific liver tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * ALP \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN |
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | From first dose to 30 days post last dose (Up to 60 months) | Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * TSH value \> ULN and * with baseline TSH value \<= ULN * with at least one FT3/FT4 test value \< LLN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \>= LLN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test. * TSH \< LLN and * with baseline TSH value \>= LLN * with at least one FT3/FT4 test value \> ULN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \<= ULN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test |
| Number of Participants Who Died | Up to 60 months | Number of participants who died in each arm. |
| Duration of Response (DOR) | From the date of first dose to the date of the first disease progression or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months) | Duration of Response (DOR) based on Blinded Independent Central Review (BICR) and investigator is defined as the time between the date of first documented complete response (CR) or partial response (PR) and the date of the first disease progression, per RECIST 1.1, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Czechia, France, Germany, Italy, Norway, Poland, Puerto Rico, Singapore, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
274 participants randomized and 271 treated.
Participants by arm
| Arm | Count |
|---|---|
| BMS986213 + Chemotherapy BMS986213 Q3W + Investigator Choice (IC) Chemotherapy | 138 |
| Nivolumab + Chemotherapy Nivolumab Q3W + Investigator Choice (IC) Chemotherapy | 136 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-treatment | Other reasons | 1 | 0 |
| Pre-treatment | Participant no longer met study criteria | 1 | 1 |
| Treatment | Administrative reasons by sponsor | 1 | 0 |
| Treatment | Adverse Event unrelated to Study Drug | 7 | 6 |
| Treatment | Completed Treatment | 0 | 2 |
| Treatment | Death | 11 | 9 |
| Treatment | Disease Progression | 85 | 97 |
| Treatment | maximum clinical benefit | 0 | 2 |
| Treatment | Other reasons | 10 | 8 |
| Treatment | Participant no longer meets study criteria | 1 | 0 |
| Treatment | Poor/Non-compliance | 1 | 0 |
| Treatment | Study Drug Toxicity | 19 | 9 |
| Treatment | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | BMS986213 + Chemotherapy | Nivolumab + Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 59.4 Years STANDARD_DEVIATION 12.1 | 61.8 Years STANDARD_DEVIATION 11.3 | 60.6 Years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 10 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 80 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 48 Participants | 46 Participants | 94 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian Indian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Chinese | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 128 Participants | 122 Participants | 250 Participants |
| Sex: Female, Male Female | 44 Participants | 38 Participants | 82 Participants |
| Sex: Female, Male Male | 94 Participants | 98 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 122 / 138 | 118 / 136 |
| other Total, other adverse events | 130 / 136 | 133 / 135 |
| serious Total, serious adverse events | 110 / 136 | 100 / 135 |
Outcome results
BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants
The number of LAG-3 Positive (\>=1%) participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized LAG-3 positive (\>=1%) participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions
Time frame: Up to 25 months
Population: All randomized LAG-3 positive (\>=1%) participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS986213 + Chemotherapy | BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants | 48.5 Percentage of Participants |
| Nivolumab + Chemotherapy | BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants | 61.2 Percentage of Participants |
BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection
The number of LAG-3 Positive (\>=1%) participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized LAG-3 positive (\>=1%) participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)
Population: All randomized LAG-3 positive (\>=1%) participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS986213 + Chemotherapy | BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection | 27.8 Percentage of Participants |
| Nivolumab + Chemotherapy | BICR-Assessed Objective Response Rate (ORR) in Randomized LAG-3 Positive (>=1 %) Participants - Extended Collection | 43.9 Percentage of Participants |
Duration of Response (DOR)
Duration of Response (DOR) based on Blinded Independent Central Review (BICR) and investigator is defined as the time between the date of first documented complete response (CR) or partial response (PR) and the date of the first disease progression, per RECIST 1.1, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions
Time frame: From the date of first dose to the date of the first disease progression or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)
Population: All randomized responders with LAG-3 positive (\>=1%), and all randomized responders with LAG-3 negative (\<1%), and all randomized responders
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Duration of Response (DOR) | BICR-assessed with LAG-3 expression >=1% | 7.72 Months |
| BMS986213 + Chemotherapy | Duration of Response (DOR) | BICR-assessed with LAG-3 expression <1% | 5.44 Months |
| BMS986213 + Chemotherapy | Duration of Response (DOR) | BICR-assessed Overall | 5.68 Months |
| BMS986213 + Chemotherapy | Duration of Response (DOR) | Investigator-assessed with LAG-3 expression >=1% | 6.21 Months |
| BMS986213 + Chemotherapy | Duration of Response (DOR) | Investigator-assessed with LAG-3 expression <1% | 5.54 Months |
| BMS986213 + Chemotherapy | Duration of Response (DOR) | Investigator-assessed Overall | 5.88 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | Investigator-assessed with LAG-3 expression <1% | 8.31 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | BICR-assessed with LAG-3 expression >=1% | 10.78 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | Investigator-assessed with LAG-3 expression >=1% | 10.28 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | BICR-assessed with LAG-3 expression <1% | 5.55 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | Investigator-assessed Overall | 9.92 Months |
| Nivolumab + Chemotherapy | Duration of Response (DOR) | BICR-assessed Overall | 6.93 Months |
Number of Participants Who Died
Number of participants who died in each arm.
Time frame: Up to 60 months
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS986213 + Chemotherapy | Number of Participants Who Died | 122 Participants |
| Nivolumab + Chemotherapy | Number of Participants Who Died | 118 Participants |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with any grade adverse events (AEs), serious adverse events (SAE), and adverse events leading to discontinuation using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v 5.0). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization, results in significant disability, is a birth defect, or is an important medical event.
Time frame: From first dose to 30 days post last dose (Up to 60 months)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) | 135 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs) | 99 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events leading to discontinuation | 76 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) | 135 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs) | 87 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events leading to discontinuation | 56 Participants |
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
Number of participants with laboratory abnormalities in specific liver tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * ALP \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Time frame: From first dose to 30 days post last dose (Up to 60 months)
Population: All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 31 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 12 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 4 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 2 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 6 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 50 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 1.5xULN WITHIN ONE DAY | 5 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 1.5xULN WITHIN 30 DAYS | 5 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 2xULN WITHIN ONE DAY | 4 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 2xULN WITHIN 30 DAYS | 4 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 1.5xULN WITHIN 30 DAYS | 2 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 14 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 56 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 5 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 2xULN WITHIN 30 DAYS | 2 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 1 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 1.5xULN WITHIN ONE DAY | 2 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | CONCURRENT ALT OR AST ELEVATION > 3xULN WITH TOTAL BILIRUBIN > 2xULN WITHIN ONE DAY | 2 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 3 Participants |
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * TSH value \> ULN and * with baseline TSH value \<= ULN * with at least one FT3/FT4 test value \< LLN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \>= LLN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test. * TSH \< LLN and * with baseline TSH value \>= LLN * with at least one FT3/FT4 test value \> ULN within 2-week window after the abnormal TSH test * with all FT3/FT4 test values \<= ULN within 2-week window after the abnormal TSH test * with FT3/FT4 missing within 2-week window after the abnormal TSH test
Time frame: From first dose to 30 days post last dose (Up to 60 months)
Population: All treated participants with thyroid stimulating hormone (TSH) abnormality measurement
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 39 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 35 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN | 24 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 15 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 TEST MISSING | 18 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 42 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH TSH >= LLN AT BASELINE | 40 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN | 22 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 12 Participants |
| BMS986213 + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 19 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN | 11 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 43 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 26 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 33 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 11 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN | 20 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH TSH >= LLN AT BASELINE | 22 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 19 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 10 Participants |
| Nivolumab + Chemotherapy | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 TEST MISSING | 24 Participants |
Objective Response Rate (ORR)
Objective response rate (ORR) based on Blinded Independent Central Review (BICR) and Investigator assessments is defined as the number of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of randomized participants in each arm; recorded between randomization date and the date of objectively documented progression \[per RECISIT 1.1\], death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. CR= Disappearance of all target lesions PR= At least a 30% decrease in the sum of diameters of target lesions Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From randomization date to the date of objectively documented progression, death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)
Population: All randomized LAG-3 positive (\>=1%) participants, and all randomized LAG-3 negative (\<1%) participants, and all randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Objective Response Rate (ORR) | BICR-assessed Overall | 27.5 Percentage of participants |
| BMS986213 + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed with LAG-3 expression <1% | 36.6 Percentage of participants |
| BMS986213 + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed with LAG-3 expression >=1% | 53.6 Percentage of participants |
| BMS986213 + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed Overall | 48.6 Percentage of participants |
| BMS986213 + Chemotherapy | Objective Response Rate (ORR) | BICR-assessed with LAG-3 expression <1% | 26.8 Percentage of participants |
| Nivolumab + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed Overall | 50.7 Percentage of participants |
| Nivolumab + Chemotherapy | Objective Response Rate (ORR) | BICR-assessed with LAG-3 expression <1% | 36.8 Percentage of participants |
| Nivolumab + Chemotherapy | Objective Response Rate (ORR) | BICR-assessed Overall | 41.9 Percentage of participants |
| Nivolumab + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed with LAG-3 expression >=1% | 54.1 Percentage of participants |
| Nivolumab + Chemotherapy | Objective Response Rate (ORR) | Investigator-assessed with LAG-3 expression <1% | 42.1 Percentage of participants |
Overall Survival (OS)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.
Time frame: From the date of randomization to the date of death due to any cause (Up to 63 months)
Population: All randomized LAG-3 positive (\>=1%) participants, and all randomized LAG-3 negative (\<1%) participants, and all randomized participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Overall Survival (OS) | LAG-3 Expression >=1% | 14.19 Months |
| BMS986213 + Chemotherapy | Overall Survival (OS) | LAG-3 Expression <1% | 9.72 Months |
| BMS986213 + Chemotherapy | Overall Survival (OS) | Overall | 12.65 Months |
| Nivolumab + Chemotherapy | Overall Survival (OS) | LAG-3 Expression >=1% | 14.98 Months |
| Nivolumab + Chemotherapy | Overall Survival (OS) | LAG-3 Expression <1% | 15.51 Months |
| Nivolumab + Chemotherapy | Overall Survival (OS) | Overall | 15.15 Months |
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR) and Investigator is defined as the time between the date of randomization and the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first. Participants who die without a reported prior progression (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Progression=At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From the date of randomization to the first date of documented progression, or death due to any cause, or date of subsequent anticancer therapy, whichever occurs first (Up to 63 months)
Population: All randomized LAG-3 positive (\>=1%) participants, and all randomized LAG-3 negative (\<1%) participants, and all randomized participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed Overall | 7.13 Months |
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed LAG-3 Expression >=1% | 7.26 Months |
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed LAG-3 Expression <1% | 6.80 Months |
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed LAG-3 Expression >=1% | 6.97 Months |
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed LAG-3 Expression <1% | 5.39 Months |
| BMS986213 + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed Overall | 6.64 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed LAG-3 Expression <1% | 9.69 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed LAG-3 Expression >=1% | 8.31 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed LAG-3 Expression >=1% | 10.84 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | Investigator-assessed Overall | 8.31 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed LAG-3 Expression <1% | 10.45 Months |
| Nivolumab + Chemotherapy | Progression-Free Survival (PFS) | BICR-assessed Overall | 10.45 Months |