CANCER, NOS Clinical Trial
Official title:
A Phase 1 Study of BMS-986015, an Anti-KIR Monoclonal Antibody, Administered With Ipilimumab, an Anti-CTLA4 Monoclonal Antibody, in Subjects With Select Advanced Solid Tumors
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.
| Status | Completed |
| Enrollment | 22 |
| Est. completion date | April 2015 |
| Est. primary completion date | April 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com. 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 |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | The Ohio State University | Columbus | Ohio |
| United States | University Of Minnesota | Minneapolis | Minnesota |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Memorial Sloan Kettering Cancer Ctr | New York | New York |
| United States | H. Lee Moffitt Cancer Center & Research Institute | Tampa | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Bristol-Myers Squibb |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Safety as measured by the rate of adverse events, and serious adverse events | Approximately 510 days | Yes | |
| Secondary | 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 | No | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes |