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

September 16, 2025 updated by: Bristol-Myers Squibb

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Local Institution - 0007
    • Ontario
      • Hamilton, Ontario, Canada, L8V5C2
        • Local Institution - 0011
      • Ottawa, Ontario, Canada, K1H 8L6
        • Local Institution - 0005
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution - 0006
  • France
      • Marseille, France, 13385
        • Local Institution - 0018
      • Toulouse, France, 31059
        • Local Institution - 0019
    • Aquitaine
      • Bordeaux, Aquitaine, France, 33076
        • Local Institution - 0015
    • Paris
      • Villejuif, Paris, France, 94800
        • Local Institution - 0014
  • Spain
      • Madrid, Spain, 28040
        • Local Institution - 0022
      • Madrid, Spain, 28050
        • Local Institution - 0023
    • Andalusia
      • Málaga, Andalusia, Spain, 29010
        • Local Institution - 0024
    • Madrid, Comunidad de
      • Madrid, Madrid, Comunidad de, Spain, 28009
        • Local Institution - 0025
  • Switzerland
      • Basel, Switzerland, 4031
        • Local Institution - 0012
      • Geneva, Switzerland, 1205
        • Local Institution - 0020
    • Canton of St. Gallen
      • Sankt Gallen, Canton of St. Gallen, Switzerland, 9007
        • Local Institution - 0021
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 0010
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Local Institution - 0001
    • Texas
      • Houston, Texas, United States, 77030
        • Local Institution - 0003

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: BMS-986408 Monotherapy
Drug: BMS-986408
Specified dose on specified days
Experimental: Part 2: BMS-986408 in combination with nivolumab
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Drug: BMS-986408
Specified dose on specified days
Experimental: Part 2: BMS-986408 in combination with nivolumab and ipilimumab
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016
  • Yervoy
Drug: BMS-986408
Specified dose on specified days
Experimental: Part 2: BMS-986408 in combination with nivolumab and chemotherapy
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Drug: BMS-986408
Specified dose on specified days
Biological: Platinum-doublet chemotherapy
Specified dose on specified days
Other Names:
  • PDCT
  • carbplatin, paclitaxel, pemetrexed, cisplatin
Experimental: Part 2: BMS-986408 in combination with rabeprazole
Drug: BMS-986408
Specified dose on specified days
Drug: Rabeprazole
Specified dose on specified days
Experimental: Part 3: BMS-986408 in combination with nivolumab
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Drug: BMS-986408
Specified dose on specified days
Experimental: Part 3: BMS-986408 in combination with nivolumab and chemotherapy
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Drug: BMS-986408
Specified dose on specified days
Biological: Platinum-doublet chemotherapy
Specified dose on specified days
Other Names:
  • PDCT
  • carbplatin, paclitaxel, pemetrexed, cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From first dose (Day 1) till 28 days
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.
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)
From first dose (Day 1) until 100 days after the last dose (Up to approximately 15 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of BMS-986408
Time Frame: Day 1 and 15 of Cycle 1 (Each cycle is of 28 days)
Blood samples were collected to assess pharmacokinetic parameters
Day 1 and 15 of Cycle 1 (Each cycle is of 28 days)
Time to Maximum Observed Plasma Concentration (Tmax) of BMS-986408
Time Frame: Day 1 and 15 of Cycle 1 (Each cycle is of 28 days)
Blood samples were collected to assess pharmacokinetic parameters
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)]
Time Frame: Day 1 and 15 of Cycle 1 (Each cycle is of 28 days)
Blood samples were collected to assess pharmacokinetic parameters.
Day 1 and 15 of Cycle 1 (Each cycle is of 28 days)
Objective Response Rate (ORR) Per RECIST v1.1
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)

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.
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
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)

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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2022

Primary Completion (Actual)

August 22, 2024

Study Completion (Actual)

July 24, 2025

Study Registration Dates

First Submitted

June 2, 2022

First Submitted That Met QC Criteria

June 2, 2022

First Posted (Actual)

June 7, 2022

Study Record Updates

Last Update Posted (Estimated)

October 3, 2025

Last Update Submitted That Met QC Criteria

September 16, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA099-003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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