Study of BMS-986158 in Subjects With Select Advanced Cancers

Advanced Tumors Clinical Trial

— BET  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02419417
• Other study ID #: CA011-001
• Secondary ID: 2015-000324-29
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 19, 2015
• Est. completion date: March 17, 2021

Study information

• Verified date: May 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: March 17, 2021
• Est. primary completion date: March 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Tumors

Intervention

Drug:
• BMS-986158
Specified dose on specified days

Biological:
• Nivolumab
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
France	Local Institution	Lyon Cedex 08
France	Local Institution	Villejuif
Spain	H. Univ. Vall dHebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
United States	University Of Colorado	Aurora	Colorado
United States	Dana Farber Cancer Institute.	Boston	Massachusetts
United States	City Of Hope National Medical Center	Duarte	California
United States	Institute for Translational Oncology Research-ITOR	Greenville	South Carolina
United States	Univ. Of Pa	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose to 30 days following last dose (up to approximately 29 months)
Primary	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	From first dose to 30 days following last dose (up to approximately 29 months)
Secondary	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.	From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
Secondary	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)	From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
Secondary	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.	From date of first response to date of first objectively documented disease progression or death (up to approximately 42 weeks)
Secondary	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.	From first dose to date of first objectively documented disease progression or death (up to approximately 28 months)
Secondary	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	From first dose to 12 weeks, to 24 weeks, and to 48 weeks after first dose
Secondary	Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	Time of Maximum Observed Plasma Concentration (Tmax) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	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	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	Apparent Terminal Phase Half-Life (T-HALF) - Single Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	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	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	Apparent Total Body Clearance (CLT/F) - Single Dose Administration	Values are reported only for the parent BMS-986158	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	Apparent Volume of Distribution of Terminal Phase (Vz/F) - Single Dose Administration	Values are reported only for the parent BMS-986158	From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
Secondary	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)	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)
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) - 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)	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)
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) - 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)	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)
Secondary	Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - 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)	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)
Secondary	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)	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)
Secondary	Concentration at the End of Dosing Interval (C24) - 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)	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)
Secondary	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	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)
Secondary	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.	Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
Secondary	Effective Elimination Half-Life (Effective T-HALF) - Multiple Dose Administration	Values are reported separately for the parent BMS-986158 and its metabolite BMT-161485.	Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
Secondary	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)	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)
Secondary	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)	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)
Secondary	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
Secondary	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)	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)
Secondary	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.	From Cycle 1 Day 1 to last dosing day in Cycle 2 (C2D8 for Schedule A, C2D14 for Schedule B, C2D7 for Schedule C).

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