Study of BMS-986158 in Subjects With Select Advanced Cancers (BET)
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| ClinicalTrials.gov Identifier: NCT02419417 |
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Recruitment Status :
Completed
First Posted : April 17, 2015
Results First Posted : June 16, 2022
Last Update Posted : June 16, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Tumors | Drug: BMS-986158 Biological: Nivolumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 83 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | June 19, 2015 |
| Actual Primary Completion Date : | March 17, 2021 |
| Actual Study Completion Date : | March 17, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Monotherapy Treatment
Patients treated at various doses and schedules
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Drug: BMS-986158
Specified dose on specified days |
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Experimental: Combination Therapy
Patients treated at selected doses and schdules
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Drug: BMS-986158
Specified dose on specified days Biological: Nivolumab Specified dose on specified days
Other Names:
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- 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.
- 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
- 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.
- 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)
- 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.
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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
- 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.
- 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.
- 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)
- 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)
- 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 [ 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)
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02419417
| United States, California | |
| City Of Hope National Medical Center | |
| Duarte, California, United States, 91010 | |
| United States, Colorado | |
| University Of Colorado | |
| Aurora, Colorado, United States, 80045 | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute. | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Oregon | |
| Oregon Health & Science University | |
| Portland, Oregon, United States, 97239 | |
| United States, Pennsylvania | |
| Univ. Of Pa | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, South Carolina | |
| Institute for Translational Oncology Research-ITOR | |
| Greenville, South Carolina, United States, 29605 | |
| Australia, Victoria | |
| Nucleus Network | |
| Melbourne, Victoria, Australia, 3004 | |
| Canada, Ontario | |
| The Ottawa Hospital Cancer Centre | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| France | |
| Local Institution | |
| Lyon Cedex 08, France, 69373 | |
| Local Institution | |
| Villejuif, France, 94800 | |
| Spain | |
| H. Univ. Vall dHebron | |
| Barcelona, Spain, 08035 | |
| Centro Integral Oncologico Clara Campal | |
| Madrid, Spain, 28050 | |
| Clinica Universidad de Navarra | |
| Pamplona, Spain, 31008 | |
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02419417 |
| Other Study ID Numbers: |
CA011-001 2015-000324-29 ( EudraCT Number ) |
| First Posted: | April 17, 2015 Key Record Dates |
| Results First Posted: | June 16, 2022 |
| Last Update Posted: | June 16, 2022 |
| Last Verified: | May 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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