Safety Study of BMS-986015 (Anti-KIR) in Combination With Ipilimumab in Subjects With Selected Advanced Tumor
- Registration Number
- NCT01750580
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
To assess the safety and tolerability, characterize the dose-limiting toxicities (DLTs), and identify the maximally tolerated dose (MTD) of BMS-986015 given in combination with ipilimumab in subjects with select advanced (metastatic and/or unresectable) solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
Inclusion Criteria
- Histologic confirmation of one of the following solid tumors that is advanced (unresectable or metastatic) for dose escalation or cohort expansion:Non-Small Cell Lung Cancer (NSCLC), Castrate Resistant Prostate Cancer (CRPC), Melanoma (MEL)
- At least one measurable lesion at baseline by Computed tomography (CT) or Magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- Biopsies: Subjects in the melanoma cohort must have at least 1 tumor site that can be biopsied at acceptable clinical risk
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Estimated life expectancy of ≥ 12 weeks
- White blood cell (WBC) ≥2000/μL, Neutrophils ≥1500/μL, Platelets ≥ 100x1000/μL, Hemoglobin ≥ 8.5 g/dL, creatinine ≤ 1.5 X upper limit of normal (ULN) mL/min, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3x ULN
- Normal thyroid function or be on stable hormone supplementation
Exclusion Criteria
- Participation in any prior clinical study with BMS-936558 or ipilimumab that has overall survival listed as a primary/co-primary endpoint
- Subjects with known or suspected brain metastasis
- Subjects with active autoimmune disease, uncontrolled or significant cardiovascular disease
- Prior therapy with anti- Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) antibody or anti- Killer cell immunoglobulin-like receptor (KIR) antibody
- Grade 2 neuropathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1: Lirilumab + Ipilimumab Ipilimumab Lirilumab and Ipilimumab on specific days Arm 1: Lirilumab + Ipilimumab Lirilumab Lirilumab and Ipilimumab on specific days
- Primary Outcome Measures
Name Time Method Safety as measured by the rate of adverse events, and serious adverse events Approximately 510 days
- Secondary Outcome Measures
Name Time Method The maximum observed serum concentration (Cmax) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2. (EOI is end of infusion, EOT is end of treatment Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Apparent volume of distribution at steady state (Vss) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Efficacy as measured by tumor assessment Assessed from the start of treatment (ay 1) to the end of treatment (week 60) and for 90 days in follow-up The time of maximum observed serum concentration (Tmax) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, EOT, follow-up 1 and follow-up 2 Apparent total body clearance (CL) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Serum half-life (T-HALF) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Trough observed serum concentration (Cmin) of BMS-986015 and Ipilimumab up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2 Immunogenicity as measured by the incidence of Ipilimumab and anti-Killer cell immunoglobulin-like receptor (KIR) (BMS-986015) anti-drug antibodies (ADA) up to 11 timepoints during Weeks 1, 3, 4, 10, 13, 24, 36,48, 60, follow-up 1 and follow-up 2
Trial Locations
- Locations (6)
The Ohio State University
🇺🇸Columbus, Ohio, United States
University Of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Memorial Sloan Kettering Cancer Ctr
🇺🇸New York, New York, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States