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Completed

NCT Number: NCT02419417

Study of BMS-986158 in Subjects With Select Advanced Cancers

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

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Key information

Conditions

Advanced Tumors

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Nucleus Network, Melbourne, Victoria, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BMS-986158

Drug

Specified dose on specified days

Nivolumab

Biological

Specified dose on specified days

Other names: BMS-936558, Opdivo

Primary outcomes

  1. Number of Participants Experiencing Adverse Events

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

    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.

  2. Number of Participants With Abnormal Hepatic Test Values

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

    Number of participants experiencing abnormal hepatic function, as measured by different parameters.

    ALT = Alanine aminotransferase AST = Aspartate aminotransferase ULN = Upper Limit of Normal

Secondary outcomes

  1. Best Overall Response (BOR)

    Time frame: From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)

    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.

  2. Objective Response Rate (ORR)

    Time frame: From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)

    ORR is defined as the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR)

  3. Duration of Response (DOR)

    Time frame: From date of first response to date of first objectively documented disease progression or death (up to approximately 42 weeks)

    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.

  4. Progression Free Survival (PFS)

    Time frame: From first dose to date of first objectively documented disease progression or death (up to approximately 28 months)

    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.

  5. Progression Free Survival Rate (PFSR)

    Time frame: From first dose to 12 weeks, to 24 weeks, and to 48 weeks after first dose

    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

  6. Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485

  7. Time of Maximum Observed Plasma Concentration (Tmax) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485

  8. Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485

  9. Apparent Terminal Phase Half-Life (T-HALF) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485

  10. Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485

  11. Apparent Total Body Clearance (CLT/F) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported only for the parent BMS-986158

  12. Apparent Volume of Distribution of Terminal Phase (Vz/F) - Single Dose Administration

    Time frame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration

    Values are reported only for the parent BMS-986158

  13. Maximum Observed Plasma Concentration (Cmax) - 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)

    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)

  14. 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)

    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)

  15. 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)

    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)

  16. 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)

    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)

  17. Minimum Observed Concentration Within a Dosing Interval (Cmin) - 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)

    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)

  18. 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)

    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)

  19. Trough Observed Plasma Concentration (Ctrough) - Multiple Dose Administration

    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)

    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

  20. Accumulation Index (AI) - Multiple Dose Administration

    Time frame: Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)

    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.

  21. Effective Elimination Half-Life (Effective T-HALF) - Multiple Dose Administration

    Time frame: Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)

    Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485.

  22. Ratio of Metabolite (BMT-161485) Maximum Observed Plasma Concentration (Cmax) to Parent (BMS-986158) Cmax - 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)

    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)

  23. 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

    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)

    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)

  24. 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

  25. 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

    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)

    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)

  26. Change From Baseline in Electrocardiogram Parameter QTcF

    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).

    QT Interval corrected for Fridericia's Formula. Change from baseline is calculated from pre-dose at the indicated timepoints.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

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

Acronym: BET

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Apr 17, 2015
Registry last updated
Jun 16, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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