Study of BMS-986158 in Subjects With Select Advanced Cancers

Phase 2CompletedNCT02419417

Bristol-Myers Squibb83 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Tumors

Interventions

BMS-986158DRUG

Specified dose on specified days

NivolumabBIOLOGICAL

Specified dose on specified days

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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

Locations (13)

City Of Hope National Medical Center

Duarte, California, United States

University Of Colorado

Aurora, Colorado, United States

Dana Farber Cancer Institute.

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: From first dose to 30 days following last dose (up to approximately 29 months)

Secondary Outcomes

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.

Time frame: 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)

Time frame: 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.

Data from ClinicalTrials.gov

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Oregon Health & Science University

Portland, Oregon, United States

Univ. Of Pa

Philadelphia, Pennsylvania, United States

Institute for Translational Oncology Research-ITOR

Greenville, South Carolina, United States

Nucleus Network

Melbourne, Victoria, Australia

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Local Institution

Lyon, France

Local Institution

Villejuif, France

...and 3 more locations

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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.

Time frame: From Cycle 1 Day 1 to last dosing day in Cycle 2 (C2D8 for Schedule A, C2D14 for Schedule B, C2D7 for Schedule C).