Clinical trial NCT02419417: Study of BMS-986158 in Subjects With Select Advanced Cancers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Tumors
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2015-04-17
Enrollment: 83
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: From first dose to 30 days following last dose (up to approximately 29 months)
measure: Number of Participants With Abnormal Hepatic Test Values
timeFrame: From first dose to 30 days following last dose (up to approximately 29 months)
Secondary outcomes:
measure: Best Overall Response (BOR)
timeFrame: From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
measure: Objective Response Rate (ORR)
timeFrame: From first dose to date of first documented progression or subsequent therapy (up to approximately 28 months)
measure: Duration of Response (DOR)
timeFrame: From date of first response to date of first objectively documented disease progression or death (up to approximately 42 weeks)
measure: Progression Free Survival (PFS)
timeFrame: From first dose to date of first objectively documented disease progression or death (up to approximately 28 months)
measure: Progression Free Survival Rate (PFSR)
timeFrame: From first dose to 12 weeks, to 24 weeks, and to 48 weeks after first dose
measure: Maximum Observed Plasma Concentration (Cmax) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Time of Maximum Observed Plasma Concentration (Tmax) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Apparent Terminal Phase Half-Life (T-HALF) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Apparent Total Body Clearance (CLT/F) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Apparent Volume of Distribution of Terminal Phase (Vz/F) - Single Dose Administration
timeFrame: From drug administration in Cycle 1 Day 1 to 168 hours post drug administration
measure: Maximum Observed Plasma Concentration (Cmax) - Multiple Dose Administration
timeFrame: 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)
measure: Time to Maximum Observed Plasma Concentration (Tmax) - Multiple Dose Administration
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-T)) - Multiple Dose Administration
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve in One Dosing Interval (AUC(0-24)) - Multiple Dose Administration
timeFrame: 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)
measure: Minimum Observed Concentration Within a Dosing Interval (Cmin) - Multiple Dose Administration
timeFrame: 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)
measure: Concentration at the End of Dosing Interval (C24) - Multiple Dose Administration
timeFrame: 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)
measure: Trough Observed Plasma Concentration (Ctrough) - Multiple Dose Administration
timeFrame: 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)
measure: Accumulation Index (AI) - Multiple Dose Administration
timeFrame: Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
measure: Effective Elimination Half-Life (Effective T-HALF) - Multiple Dose Administration
timeFrame: Cycle 2 Day 5 (Schedule A) or Cycle 2 Day 14 (Schedule B) or Cycle 2 Day 7 (Schedule C)
measure: Ratio of Metabolite (BMT-161485) Maximum Observed Plasma Concentration (Cmax) to Parent (BMS-986158) Cmax - Multiple Dose Administration
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: Cycle 1 Day 1
measure: 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
timeFrame: 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)
measure: Change From Baseline in Electrocardiogram Parameter QTcF
timeFrame: From Cycle 1 Day 1 to last dosing day in Cycle 2 (C2D8 for Schedule A, C2D14 for Schedule B, C2D7 for Schedule C).
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City Of Hope National Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute.
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Univ. Of Pa
state: Pennsylvania
city: Greenville
country: United States
facility: Institute for Translational Oncology Research-ITOR
state: South Carolina
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Lyon Cedex 08
country: France
facility: Local Institution
city: Villejuif
country: France
facility: Local Institution
city: Barcelona
country: Spain
facility: H. Univ. Vall dHebron
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: