Study of BMS-986158 in Subjects With Select Advanced Cancers (BET)

A Phase I/IIa Trial With BMS-986158, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, as Monotherapy or in Combination With Nivolumab in Subjects With Selected Advanced Solid Tumors or Hematologic Malignancies

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-986158 in subjects with select advanced cancers

Study Overview

• Status: Completed
• Conditions: Advanced Tumors
• Intervention / Treatment: Biological: Nivolumab; Drug: BMS-986158

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
• France
  • Lyon Cedex 08, France, 69373
    • Local Institution
  • Villejuif, France, 94800
    • Local Institution
• Spain
  • Barcelona, Spain, 08035
    • H. Univ. Vall dHebron
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ. Of Pa
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Institute for Translational Oncology Research-ITOR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have select advanced cancers with specific genetic profiles
• Must have received appropriate standard of care
• At least one measurable lesion at baseline
• Expected to have life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) of 0 to 1

Exclusion Criteria:

• Concomitant second malignancies
• Uncontrolled or significant cardiovascular disease
• Inadequate bone marrow function
• Chronic gastrointestinal illness
• Prior treatment with Bromodomain and Extra-Terminal (BET) inhibitor

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Treatment; Patients treated at various doses and schedules	Drug: BMS-986158; Specified dose on specified days
Experimental: Combination Therapy; Patients treated at selected doses and schdules	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Drug: BMS-986158; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Adverse Events	Number of participants experiencing different types of events, including Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation and deaths. Events are classified based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 30 days following last dose (up to approximately 29 months)
Number of Participants With Abnormal Hepatic Test Values	Number of participants experiencing abnormal hepatic function, as measured by different parameters. ALT = Alanine aminotransferase AST = Aspartate aminotransferase ULN = Upper Limit of Normal	From first dose to 30 days following last dose (up to approximately 29 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR)	BOR, as assessed by the investigator, is defined as the best response designation, recorded between the dates of first dose and the date of first objectively documented progression (per RECIST v1.1 for solid tumors, Lugano 2014 criteria for hematologic malignancies or PCWG3 for prostate cancer) or the date of subsequent therapy, whichever occurs first.	From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR)	From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
Duration of Response (DOR)	DOR is defined as the time between the date of first response and the date of the first objectively documented disease progression (as determined by RECIST v1.1 for solid tumors, Lugano 2014 criteria for hematologic malignancies, or PCWG3 (including PSA assessments) for prostate cancer [CRPC or NEPC]), or death due to any cause, whichever occurs first.	From date of first response to date of first objectively documented disease progression or death (up to approximately 42 weeks)
Progression Free Survival (PFS)	PFS is defined as the time from the first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause.	From first dose to date of first objectively documented disease progression or death (up to approximately 28 months)
Progression Free Survival Rate (PFSR)	PFSR is defined as the percentage of participants who remain progression free and surviving at the specified timepoints (12 weeks, 24 weeks, and 48 weeks). Reported values are estimates derived from Kaplan-Meier analyses	From first dose to 12 weeks, to 24 weeks, and to 48 weeks after first dose
Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Time of Maximum Observed Plasma Concentration (Tmax) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Apparent Terminal Phase Half-Life (T-HALF) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Apparent Total Body Clearance (CLT/F) - Single Dose Administration	Values are reported only for the parent BMS-986158	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Apparent Volume of Distribution of Terminal Phase (Vz/F) - Single Dose Administration	Values are reported only for the parent BMS-986158	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Maximum Observed Plasma Concentration (Cmax) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Time to Maximum Observed Plasma Concentration (Tmax) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Minimum Observed Concentration Within a Dosing Interval (Cmin) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are reported only for the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Concentration at the End of Dosing Interval (C24) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Trough Observed Plasma Concentration (Ctrough) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485. Values are also reported separately for the first and last collection	From Cycle (C)2 Day (D)2 to C2D5 (Schedule A) or from C2D14 to C4D8 (Schedule B) or from C2D7 to C8D8 (Schedule C)
Accumulation Index (AI) - Multiple Dose Administration	AI is defined as the ratio of an exposure measure at steady-state to that after the first dose. Reported exposure measures include Cmax, C24 and AUC24. Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485.	Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
Effective Elimination Half-Life (Effective T-HALF) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485.	Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
Ratio of Metabolite (BMT-161485) Maximum Observed Plasma Concentration (Cmax) to Parent (BMS-986158) Cmax - Multiple Dose Administration	Values are reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Ratio of Metabolite (BMT-161485) Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) to Parent (BMS-986158) AUC(0-T) - Multiple Dose Administration	Values are reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Ratio of Metabolite (BMT-161485) Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) to Parent (BMS-986158) AUC(INF) - Multiple Dose Administration		Cycle 1 Day 1
Ratio of Metabolite (BMT-161485) Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) to Parent (BMS-986158) AUC(0-24) - Multiple Dose Administration	Values are reported separately for Cycle 1 Day 1 and the latest collection timepoint available (Cycle 2 Day 5 for Schedule A, Cycle 2 day 14 for Schedule B, Cycle 2 Day 7 for Schedule C)	From Cycle 1 Day 1 to Cycle 2 Day 5 (Schedule A) or to Cycle 2 Day 14 (Schedule B) or to Cycle 2 Day 7 (Schedule C)
Change From Baseline in Electrocardiogram Parameter QTcF	QT Interval corrected for Fridericia's Formula. Change from baseline is calculated from pre-dose at the indicated timepoints.	From Cycle 1 Day 1 to last dosing day in Cycle 2 (C2D8 for Schedule A, C2D14 for Schedule B, C2D7 for Schedule C).

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2015
• Primary Completion (Actual): March 17, 2021
• Study Completion (Actual): March 17, 2021

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 14, 2015
• First Posted (Estimate): April 17, 2015

Study Record Updates

• Last Update Posted (Actual): June 16, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA011-001; 2015-000324-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No