Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients treated at various doses and schedules

Patients treated at selected doses and schdules

BMS-986158

Bristol-Myers Squibb

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

Study of BMS-986158 in Subjects With Select Advanced Cancers

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

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 experiencing abnormal hepatic function, as measured by different parameters.

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

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.

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

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.

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.

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

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

Values are reported only for the parent BMS-986158

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)

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)

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

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.

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

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)

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

Single dose of BMS-986158 at 0.75 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 1 Schedule A - BMS-986158 0.75 mg

Single dose of BMS-986158 at 1.25 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 1 Schedule A - BMS-986158 1.25 mg

Single dose of BMS-986158 at 2 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 1 Schedule A - BMS-986158 2 mg

Single dose of BMS-986158 at 3 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 1 Schedule A - BMS-986158 3 mg

Single dose of BMS-986158 at 4.5 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 1 Schedule A - BMS-986158 4.5 mg

Single dose of BMS-986158 at 2 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 14 consecutive days, followed by a 7 days rest period, on a 21 days cycle

Part 1 Schedule B - BMS-986158 2 mg

Single dose of BMS-986158 at 3 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 14 consecutive days, followed by a 7 days rest period, on a 21 days cycle

Part 1 Schedule B - BMS-986158 3 mg

Single dose of BMS-986158 at 2 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 7 consecutive days, followed by a 14 days rest period, on a 21 days cycle

Part 1 Schedule C - BMS-986158 2 mg

Single dose of BMS-986158 at 3 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 7 consecutive days, followed by a 14 days rest period, on a 21 days cycle

Part 1 Schedule C - BMS-986158 3 mg

Single dose of BMS-986158 at 4.5 mg. Approximately 7 days later, BMS-986158 is administered at the same dose QD for 7 consecutive days, followed by a 14 days rest period, on a 21 days cycle

Part 1 Schedule C - BMS-986158 4.5 mg

BMS-986158 administered at 4.5 mg QD for 5 consecutive days, followed by a 2 days resting period, for a total of 10 doses.

Then, BMS-986158 is administered at the 3.75 mg dose QD for 5 consecutive days, followed by a 2 days rest period, on a 28 days cycle

Part 2 Schedule A

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

Adverse Events (AEs)

Serious Adverse Events (SAEs)

AEs leading to discontinuation

Deaths

Number of Participants Experiencing Adverse Events

ALT OR AST > 3XULN

ALT OR AST > 5XULN

ALT OR AST > 10XULN

ALT OR AST > 20XULN

TOTAL BILIRUBIN > 2XULN

CONCURRENT ALT OR AST > 3XULN AND BILIRUB > 2XULN WITHIN 1 DAY

CONCURRENT ALT OR AST > 3XULN AND BILIRUB > 2XULN WITHIN 30 DAYS

Number of Participants With Abnormal Hepatic Test Values

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unable to determine

Best Overall Response (BOR)

Objective Response Rate (ORR)

All participants who achieved a Complete Response (CR) or Partial Response (PR)

Duration of Response (DOR)

Progression Free Survival (PFS)

12 weeks

24 weeks

48 weeks

Progression Free Survival Rate (PFSR)

Parent BMS-986158

Metabolite BMT-161485

All participants treated with BMS-986158 at 0.75 mg dose, regardless of the dosing schedule.

BMS-986158 0.75 mg

All participants treated with BMS-986158 at 1.25 mg dose, regardless of the dosing schedule.

BMS-986158 1.25 mg

All participants treated with BMS-986158 at 2 mg dose, regardless of the dosing schedule.

BMS-986158 2 mg

All participants treated with BMS-986158 at 3 mg dose, regardless of the dosing schedule.

BMS-986158 3 mg

All participants treated with BMS-986158 at 4.5 mg dose, regardless of the dosing schedule.

BMS-986158 4.5 mg

All treated participants with available measurements

Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration

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

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

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

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

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

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

Parent BMS-986158 - Cycle 1 Day 1

Parent BMS-986158 - Latest timepoint

Metabolite BMT-161485 - Cycle 1 Day 1

Metabolite BMT-161485 -Latest timepoint

All treated participants with available measurements. PK data not collected for the participant in Part 2 Schedule A cohort

Maximum Observed Plasma Concentration (Cmax) - Multiple Dose Administration

Parent BMS-986158 - Cycle 1 day 1

Time to Maximum Observed Plasma Concentration (Tmax) - Multiple Dose Administration

Metabolite BMT-161485 - Cycle 1 day 1

Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) - Multiple Dose Administration

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

Minimum Observed Concentration Within a Dosing Interval (Cmin) - Multiple Dose Administration

Concentration at the End of Dosing Interval (C24) - Multiple Dose Administration

Parent BMS-986158 - First collection

Parent BMS-986158 -Last collection

Metabolite BMT-161485 - First collection

Metabolite BMT-161485 - Last collection

Trough Observed Plasma Concentration (Ctrough) - Multiple Dose Administration

Parent BMS-986158 - Cmax

Parent BMS-986158 - C24

Parent BMS-986158 - AUC24

Metabolite BMT-161485 - Cmax

Metabolite BMT-161485 - C24

Metabolite BMT-161485 - AUC24

Accumulation Index (AI) - Multiple Dose Administration

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

Cycle 1 Day 1

Latest timepoint

Ratio of Metabolite (BMT-161485) Maximum Observed Plasma Concentration (Cmax) to Parent (BMS-986158) Cmax - Multiple Dose Administration

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

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

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

All treated participants with available measurements at the indicated timepoints. PK data not collected for the participant in Part 2 Schedule A cohort

Spots Global Cancer Trial Database for Study of BMS-986158 in Subjects With Select Advanced Cancers

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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