Study of BMS-986158 in Subjects With Select Advanced Cancers
- Registration Number
- NCT02419417
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-986158 in subjects with select advanced cancers
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Monotherapy Treatment BMS-986158 Patients treated at various doses and schedules Combination Therapy BMS-986158 Patients treated at selected doses and schdules Combination Therapy Nivolumab Patients treated at selected doses and schdules
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events 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.Number of Participants With Abnormal Hepatic Test Values 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 Outcome Measures
Name Time Method Duration of Response (DOR) 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.
Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration 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
Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Single Dose Administration 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
Apparent Terminal Phase Half-Life (T-HALF) - Single Dose Administration 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
Best Overall Response (BOR) 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.
Objective Response Rate (ORR) 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)
Progression Free Survival (PFS) 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.
Progression Free Survival Rate (PFSR) 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 analysesArea Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Multiple Dose Administration 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)Time of Maximum Observed Plasma Concentration (Tmax) - Single Dose Administration 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
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) - Single Dose Administration 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
Apparent Total Body Clearance (CLT/F) - Single Dose Administration From drug administration in Cycle 1 Day 1 to 168 hours post drug administration Values are reported only for the parent BMS-986158
Apparent Volume of Distribution of Terminal Phase (Vz/F) - Single Dose Administration From drug administration in Cycle 1 Day 1 to 168 hours post drug administration Values are reported only for the parent BMS-986158
Maximum Observed Plasma Concentration (Cmax) - Multiple Dose Administration 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)Time to Maximum Observed Plasma Concentration (Tmax) - Multiple Dose Administration 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)Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) - Multiple Dose Administration 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)Minimum Observed Concentration Within a Dosing Interval (Cmin) - Multiple Dose Administration 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)Concentration at the End of Dosing Interval (C24) - Multiple Dose Administration 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)Trough Observed Plasma Concentration (Ctrough) - Multiple Dose Administration 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 collectionAccumulation Index (AI) - Multiple Dose Administration 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.Effective Elimination Half-Life (Effective T-HALF) - Multiple Dose Administration 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.
Ratio of Metabolite (BMT-161485) Maximum Observed Plasma Concentration (Cmax) to Parent (BMS-986158) Cmax - Multiple Dose Administration 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)
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 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)
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 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)
Change From Baseline in Electrocardiogram Parameter QTcF 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.
Trial Locations
- Locations (12)
Univ. Of Pa
🇺🇸Philadelphia, Pennsylvania, United States
City Of Hope National Medical Center
🇺🇸Duarte, California, United States
Institute for Translational Oncology Research-ITOR
🇺🇸Greenville, South Carolina, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Dana Farber Cancer Institute.
🇺🇸Boston, Massachusetts, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Nucleus Network
🇦🇺Melbourne, Victoria, Australia
Local Institution
🇫🇷Villejuif, France
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
H. Univ. Vall dHebron
🇪🇸Barcelona, Spain