Various Advanced Cancer
Conditions
Brief summary
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
Interventions
DRUGBMS-986115
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Subjects with a histologically or cytologically confirmed diagnosis of solid tumors, advanced or metastatic, refractory to or relapsed from standard therapies or for which there is no known effective treatment * Life expectancy of at least 3 months * Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 * Prior anti-cancer treatments are permitted (i.e., chemotherapy, radiotherapy, hormonal, or immunotherapy) * At least 4 weeks must have elapsed from last dose of prior anti-cancer therapy and the initiation of study therapy
Exclusion criteria
* Subjects with known or suspected brain metastases, primary brain tumors, or brain as the only site of disease * Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study medication * Current or recent (within 3 months of study drug administration) gastrointestinal disease such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g. infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary * Any major surgery or gastrointestinal disease that would interfere with administration of oral medications * Conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease or severe asthma, excluding inhalation steroids for maintenance. * Uncontrolled or significant cardiovascular disease * History of medically significant thromboembolic events or bleeding diathesis within the past 6 months * Inadequate bone marrow function (Absolute neutrophil count (ANC) \< 1,500 cells/mm3; Platelet count \< 100,000 cells/mm3; Hemoglobin \< 9.0 g/dL) * Inadequate hepatic function (Total bilirubin \> 1.5 times the institutional upper limit of normal (ULN) (except known Gilbert's syndrome); Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2.5 times the institutional ULN. ALT or AST up to 3 times the institutional ULN permitted if total bilirubin is normal * Uncontrolled (≥ Grade 2) hypertriglyceridemia (fasting triglycerides \> 300 mg/dL (3.42 mmol/L)) * Inadequate renal function (Blood creatinine \> 1.5 times the institutional ULN) * Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV) -1, -2 antibody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of multiple daily doses of BMS-986115 | Up to 30 days after the last dose of study medication (approximately 18 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948 | 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 | 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 | 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 | 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 | 29 timepoints up to Cycle 3 Day 1 (approximately 32 days) | — |
| Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948 | 29 timepoints up to Cycle 3 Day 1 (approximately 32 days) | — |
| Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948 | 29 timepoints up to Cycle 3 Day 1 (approximately 32 days) | — |
| Apparent volume of distribution at steady-state (Vz/F) of BMS-986115 | 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 | 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 | 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 | 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) | Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months) | 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 |
| Apparent total body clearance (CLT/F) of BMS-986115 | 29 timepoints up to Cycle 3 Day 1 (approximately 32 days) | — |
Countries
Australia, Canada, United States
Outcome results
None listed