A Phase 1/2 Study of BMS-986408 Alone and in Combination With Nivolumab or With Nivolumab and Ipilimumab in Participants With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 68
- Locations
- 35
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities (DLTs)
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Part 2: BMS-986408 in combination with nivolumab
Intervention: BMS-986408 (Drug)
Part 3: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: Platinum-doublet chemotherapy (Biological)
Part 3: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: Nivolumab (Biological)
Part 2: BMS-986408 in combination with nivolumab and ipilimumab
Intervention: Nivolumab (Biological)
Part 2: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: Platinum-doublet chemotherapy (Biological)
Part 1: BMS-986408 Monotherapy
Intervention: BMS-986408 (Drug)
Part 2: BMS-986408 in combination with nivolumab
Intervention: Nivolumab (Biological)
Part 3: BMS-986408 in combination with nivolumab
Intervention: BMS-986408 (Drug)
Part 2: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: BMS-986408 (Drug)
Part 3: BMS-986408 in combination with nivolumab
Intervention: Nivolumab (Biological)
Part 2: BMS-986408 in combination with nivolumab and ipilimumab
Intervention: Ipilimumab (Biological)
Part 2: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: Nivolumab (Biological)
Part 3: BMS-986408 in combination with nivolumab and chemotherapy
Intervention: BMS-986408 (Drug)
Part 2: BMS-986408 in combination with nivolumab and ipilimumab
Intervention: BMS-986408 (Drug)
Part 2: BMS-986408 in combination with rabeprazole
Intervention: BMS-986408 (Drug)
Part 2: BMS-986408 in combination with rabeprazole
Intervention: Rabeprazole (Drug)
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: From first dose (Day 1) till 28 days
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.
Number of Participants With Adverse Events
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
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.
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(Day 1 and 15 of Cycle 1 (Each cycle is of 28 days))
- Time to Maximum Observed Plasma Concentration (Tmax) of BMS-986408(Day 1 and 15 of Cycle 1 (Each cycle is of 28 days))
- Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration [AUC(0-T)](Day 1 and 15 of Cycle 1 (Each cycle is of 28 days))
- Objective Response Rate (ORR) Per RECIST v1.1(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(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))
