A Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

This endpoint was prespecified in the protocol to include only participants in Part 1.

A serious adverse event is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event.

This endpoint was prespecified in the protocol to include only participants in Part 1.

Dose-Limiting Toxicities (DLTs) are effects of a treatment that are serious enough to prevent an increase in dose of that treatment, as advised by the Dose Review Team. DLTs will be defined based on the incidence, intensity, and duration of AEs that are possibly related to study treatment. DLTs will include gastrointestinal, hepatic, hematologic, dermatologic, and other AEs.

This endpoint was prespecified in the protocol to include only participants in Part 1.

Number of participants with any grade adverse events (AEs) leading to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

This endpoint was prespecified in the protocol to include only participants in Part 1.

The number of participants who died due to any cause are summarized. This endpoint was prespecified in the protocol to include only participants in Part 1.

Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Laboratory tests are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

This endpoint was prespecified in the protocol to include only participants in Part 1.

Objective Response Rate per blinded independent central review (BICR) is the percentage of participants who have a confirmed complete or partial best overall response (BOR) among participants who have measurable disease at baseline. Complete Response (CR) is defined as 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) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Baseline was defined as evaluations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations. This endpoint was prespecified in the protocol to include only participants in Part 2.

Objective Response Rate per investigator is the percentage of participants who have a confirmed complete or partial best overall response (BOR) among participants who have measurable disease at baseline. Complete Response (CR) is defined as 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) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Baseline was defined as evaluations or events that occur before the date and time of the first dose of study treatment or evaluations on the same date and time of the first dose of study treatment were also considered as baseline evaluations. This endpoint was prespecified in the protocol to include only participants in Part 1.

DOR for a participant with a best overall response (BOR) of CR or PR is defined as the date of first response up to the date of the first objectively documented tumor progression by the investigator per RECIST v1.1 or death, whichever occurs first. Analysis 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 if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm.

This endpoint was prespecified in the protocol to include only participants in Part 1.

Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

AUC (0-T) represents the observed exposure to a drug (area under the concentration curve) from first exposure until the last quantifiable concentration. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Area under the concentration-time curve in 1 dosing interval. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

BMS-986253 observed serum concentration at the end of a dosing interval (Ctau). Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except Cycles 1 and 2 (1 cycle=42 days) in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group

Clearance is the rate of elimination of BMS-986253 from the blood calculated as the rate of elimination divided by serum concentration. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

BMS-986253 Average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css-avg) at steady state. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: C2D1, C3D1, C4D1 were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

AUC Accumulation Index is defined as the ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: C2D1, C3D1, C4D1 were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

BMS-986253 Cmax accumulation index (AI_Cmax). Ratio of an exposure measure at steady state to that after the first dose. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: C2D1, C3D1, C4D1 were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

Ctau is the observed serum concentration at the end of a dosing interval. Ctau accumulation index (AI_Ctau) is the ratio of an exposure measure at steady state to that after the first dose. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint. Ctau was reported on non-compartmental analysis day, which is on Cycle 1 Day1, Cycle 2 Day 1, Cycle 3 Day 1, or Cycle 4 Day 1 based on data available.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: C2D1, C3D1, C4D1 were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

BMS-986253 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure. Only Part 1 pharmacokinetic evaluable participants were pre-specified to be evaluated in this endpoint.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: C2D1, C3D1, C4D1 were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

Tmax is defined as the time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

A serum trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. Serum trough concentrations (Ctrough) of BMS-986253 will be summarized with descriptive statistics by treatment and visit.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: The timepoints listed were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

Blood samples were evaluated for development of Anti-Drug Antibody (ADA) by a validated electrochemiluminescent (ECL) immunoassay. Baseline is defined as first dose.

ADA-positive subject: A subject with at least one ADA positive-sample relative to baseline at any time after initiation of treatment.

Persistent Positive (PP): ADA-positive sample at 2 or more consecutive time points, where the first and last ADA-positive samples are at least 16 weeks apart

Not PP-Last Sample Positive: Not persistent positive with ADA-positive sample at the last sampling time point

Other Positive: Not persistent positive but some ADA-positive samples with the last sample being negative

Neutralizing Positive: At least one ADA-positive sample with neutralizing antibodies detected

ADA-negative subject: A subject with no ADA-positive sample after the initiation of treatment.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Change from baseline in IL-8 measured in pg/mL. Baseline is defined as first dose.

1 cycle=28 days for all Arms/Groups except in "Part 1: 3600Q2W + Nivo + Ipi" Arm/Group (1 cycle=42 days)

Note: Some timepoints were partial samplings only as pre-specified in the protocol and did not include a sampling for each arm.

Progression free survival (PFS) is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression by BICR or death due to any cause, whichever is earlier.

Progressive Disease (PD): 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. The appearance of one or more new lesions is also considered progression.

This endpoint was prespecified in the protocol to include only participants in Part 2.

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

This endpoint was prespecified in the protocol to include only participants in Part 2.

A serious adverse event is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event.

Number of participants with any grade adverse events (AEs) leading to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

The number of participants who died due to any cause are summarized.

Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Laboratory tests are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

This endpoint was prespecified in the protocol to include only participants in Part 2.