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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01750580
First received: December 6, 2012
Last updated: March 23, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
CANCER, NOS
Drug: Lirilumab
Drug: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety as measured by the rate of adverse events, and serious adverse events [ Time Frame: Approximately 510 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy as measured by tumor assessment [ Time Frame: Assessed from the start of treatment (ay 1) to the end of treatment (week 60) and for 90 days in follow-up ] [ Designated as safety issue: No ]
  • The maximum observed serum concentration (Cmax) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • The time of maximum observed serum concentration (Tmax) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Apparent total body clearance (CL) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Apparent volume of distribution at steady state (Vss) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Serum half-life (T-HALF) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Trough observed serum concentration (Cmin) of BMS-986015 and Ipilimumab [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Immunogenicity as measured by the incidence of Ipilimumab and anti-Killer cell immunoglobulin-like receptor (KIR) (BMS-986015) anti-drug antibodies (ADA) [ Time Frame: up to 11 timepoints during Weeks 1, 3, 4, 10, 13, 24, 36,48, 60, follow-up 1 and follow-up 2 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 125
Study Start Date: December 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Lirilumab + Ipilimumab
Lirilumab and Ipilimumab on specific days
Drug: Lirilumab
Other Names:
  • BMS-986015
  • IPH-2102
  • ANTI-KIR
Drug: Ipilimumab
Other Name: BMS-734016

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01750580

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
University Of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan Kettering Cancer Ctr
New York, New York, United States, 10065
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01750580     History of Changes
Other Study ID Numbers: CA223-002
Study First Received: December 6, 2012
Last Updated: March 23, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

ClinicalTrials.gov processed this record on March 31, 2015