The primary purpose of this study is to evaluate the safety and effectiveness of daily doses of BMS-986115 in subjects with advanced solid tumors
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Usc/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Local Institution
Parkville, Victoria, Australia
Local Institution
Vancouver, British Columbia, Canada
Local Institution
Toronto, Ontario, Canada
Safety and tolerability of multiple daily doses of BMS-986115
Measured by the frequency of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, Grade 3 or 4 AEs, deaths, laboratory abnormalities and clinically relevant electrocardiogram (ECG) changes from baseline
Time frame: Up to 30 days after the last dose of study medication (approximately 18 months)
Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
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Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Apparent total body clearance (CLT/F) of BMS-986115
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Apparent volume of distribution at steady-state (Vz/F) of BMS-986115
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Ratio of metabolite AUC(INF) to parent AUC(INF) after single dose and ratio of metabolite AUC(TAU) to parent AUC(TAU) at steady state, corrected for molecular weight (MR_AUC) of BMS-986115 and its active metabolite BMT-100948
Time frame: 29 timepoints up to Cycle 3 Day 1 (approximately 32 days)
Pharmacodynamics (PD) changes in the expression of Notch pathway-related genes, including but not limited to Hes1 and Deltex1, as determined by standard molecular methods
Time frame: 16 timepoints up to Cycle 2 Day 16 (approximately 20 days)
Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)
Assessed by: * Tumor Response based on the Investigator's assessment using RECIST v1.1 \[categorized as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD)\] * Best Overall Response (BOR), defined as the best tumor response recorded between the data of first dose and the last on-study tumor assessment (prior to any subsequent cancer therapy) * Overall Response Rate, defined as the proportion of subjects with BOR responses of CR or PR * Disease Control Rate, defined as the proportion of subjects with BOR responses of CR, PR or SD * Progression-Free Survival (or PFS), defined as time from first dose to either progressive disease, initiation of subsequent off-study therapy, or death
Time frame: Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months)