An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

An Adverse Event (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. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect.

Time frame: From first dose and within 135 days after last dose of study therapy (Up to approximately 82 months)

Population: All treated participants included all who received either study drug (BMS-986016 or Nivolumab).

Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response-evaluable population include all participants in Parts C, D1, D2 and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1, D2 and E.

DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response Evaluable Participants in Part C, D1, D2, E. Only participants with CR or PR were included in the analysis. Pre-specified to be only collected for Part C, D1, D2 and E.

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response-evaluable population include all participants in Parts C, D1, D2 and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1, D2 and E.

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose (Day 1) and up to 97 months

Population: Response-evaluable population include all participants in Parts C, D1, D2, and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1, D2 and E. Only participants with data available at the timepoint were included in the analysis.

An Adverse Event (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.

Time frame: From first dose and within 2 days of first dose of study therapy

Population: All treated participants included all who received either study drug (BMS-986016 or Nivolumab). Pre-specified to be only collected for Part D1 participants.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

Time frame: Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis. Pre-specified to be only analyzed for Part A, B, C, and D1.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

Time frame: Day 1 of Cycle 1 and 3

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis. Pre-specified to be only analyzed for Part A, B, C, and D1.

Blood samples were collected to assess anti-drug antibodies.

Time frame: predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)

Population: All treated participants with baseline and at least one post-baseline assessment of anti-drug antibodies.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). AUC Accumulation Index is a pharmacokinetic metric used to quantify how much a drug accumulates in the body after repeated dosing compared to a single dose. It is ratio of AUC Steady State (AUCss) and AUC1. AUCₛₛ is the area under the plasma concentration-time curve during a dosing interval at steady state (after repeated doses). AUC₁ is the area under the curve after a single dose. Only assessed for arm Part A/A1, B, C as pre-specified.

Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days)

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis. 0 participants analyzed as the concentration of Relatlimab was below lower limit of quantification required for assessing AI\_AUC.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). Ctrough is defined as the lowest concentration of drug in the blood immediately before the next dose is administered. Ctrough was only assessed for arm Part A/A1, B, C, D1, D2 and E as pre-specified.

Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days)

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). CLT was only assessed for arm Part A/A1, B, C as pre-specified.

Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days).

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis.

Abnormal electrocardiogram parameter included QT prolongation.

Time frame: predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)

Population: All treated participants.

The proportion of participants remaining progression free and surviving up to 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.

Time frame: Up to 12 months

Population: Response-evaluable population include all participants in Parts C, D1, and D2 who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1 and D2. Only participants with data available are included in the analysis.

The progression of participants remaining progression free and surviving up to 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression.

Time frame: Up to 12 months

Population: Response-evaluable population include all participants in Parts C, D, who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1 and D2. Only participants with data available at the timepoint were included in the analysis.

Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response-evaluable population include all participants in Parts C, D1, D2, and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1, D2 and E.

DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response Evaluable Participants in Part C, D1, D2, E. Only participants with CR or PR were included in the analysis. Pre-specified to be only collected for Part C, D1, D2 and E.

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

Population: Response-evaluable population include all participants in Parts C, D1, D2, and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part C, D1, D2 and E.

Overall survival at 1 year, and 2 years is defined as the proportion of participants who are alive at 1 year, and 2 years. Based on Kaplan-Meier Estimates.

Time frame: At 12 and 24 months after first dose

Population: Response-evaluable population include all participants in Parts C, D, and E who had a baseline tumor assessment, and one of the following: (1) at least one evaluable on-treatment tumor assessment, (2) clinical progression, or (3) death. Pre-specified to be only collected for Part D1 and D2.

Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

Time frame: Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).

Population: Relatlimab pharmacokinetic population all participants who received relatlimab and had any evaluable concentration-time data. Only participants with data available at the timepoint were included in the analysis. Pre-specified to be only analyzed for Part A, B, C, and D1.