A Study to Evaluate the Safety and Tolerability of BMS-986408 Alone and in Combination With Nivolumab or Nivolumab and Ipilimumab in Participants With Advanced Solid Tumors

Bristol-Myers Squibb68 enrolled

Overview

The primary purpose of this study is to characterize the safety profile of BMS-986408 as monotherapy and in combination with nivolumab or nivolumab and ipilimumab to establish the maximum tolerated dose (MTD). The Recommended Phase 2 Dose (RP2D) that optimizes the pharmacokinetic/pharmacodynamic (PK/PD) relationship of BMS-986408 will also be determined.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

BMS-986408DRUG

Specified dose on specified days

NivolumabBIOLOGICAL

Specified dose on specified days

IpilimumabBIOLOGICAL

Specified dose on specified days

Platinum-doublet chemotherapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants with a histologically or cytologically confirmed, advanced, unresectable/metastatic, solid malignancy of any histology measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Participants who have received, been refractory to, ineligible for, or intolerant of existing therapy(ies) known to provide clinical benefit for the condition of the participant * Participants with melanoma should have documentation of mutation status for B-type Raf proto-oncogene (BRAF) and neuroblastoma ras viral oncogene homolog (NRAS) * Participants must have experienced radiographically documented progressive disease on or after the most recent therapy Exclusion Criteria: * An active, known or suspected autoimmune disease * Conditions requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment * Current or recent gastrointestinal disease or gastrointestinal surgery that could impact the absorption of study drug * Untreated central nervous system (CNS) metastases or leptomeningeal metastasis Other protocol-defined inclusion/exclusion criteria apply

Locations (18)

Local Institution - 0010

Boston, Massachusetts, United States

Local Institution - 0001

Hackensack, New Jersey, United States

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

A Dose-Limiting Toxicity (DLT) is defined as a treatment-related adverse event that meets specific severity criteria, excluding those clearly due to disease progression or unrelated causes. DLTs include: any Grade ≥3 non-hematologic toxicity (with exceptions like transient nausea, fatigue, rash, or electrolyte imbalances), significant liver enzyme elevations, Grade 4 neutropenia \>7 days, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, febrile neutropenia, and any Grade ≥3 immune-mediated toxicity including myocarditis, myelitis, or severe skin reactions. Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization.

Time frame: From first dose (Day 1) till 28 days

Number of Participants With Adverse Events

An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.

Time frame: From first dose (Day 1) till 30 days after the last dose (Up to approximately 13 months) for Group A to C and from Day 1 untill 100 days after last dose (up to approximately 15 months) for group D

Number of Participants Who Died

Time frame: From first dose (Day 1) until 100 days after the last dose (Up to approximately 15 months)

Secondary Outcomes

Maximum Observed Plasma Concentration (Cmax) of BMS-986408

Blood samples were collected to assess pharmacokinetic parameters

Data from ClinicalTrials.gov

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Objective Response Rate (ORR) Per RECIST v1.1

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR 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 randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy or death, whichever occurs first (up to approximately 12 months)

Duration of Response Per RECIST v1.1

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 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.