Safety Study of BMS-986015 (Anti-KIR) in Combination With Ipilimumab in Subjects With Selected Advanced Tumor

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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CANCER, NOS

Intervention / Treatment
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* Drug: Lirilumab
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Lirilumab + Ipilimumab<br>Lirilumab and Ipilimumab on specific days | Drug: Lirilumab<br> <br> * Other names: ANTI-KIR;Drug: Ipilimumab<br> <br> * Other names: BMS-734016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by the rate of adverse events, and serious adverse events |  | Approximately 510 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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 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 | 
| 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 | 
| 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 | 
| 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 |