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

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.

Study Overview

• Status: Completed
• Conditions: CANCER, NOS
• Intervention / Treatment: Drug: Ipilimumab; Drug: Lirilumab

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Ctr
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Lirilumab + Ipilimumab; Lirilumab and Ipilimumab on specific days	Drug: Ipilimumab; Other Names: BMS-734016; Drug: Lirilumab; Other Names: BMS-986015; IPH-2102; ANTI-KIR

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Estimate): July 22, 2015
• Last Update Submitted That Met QC Criteria: July 20, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: CA223-002