Phase 1 Biomarker Study of Anti-PD-1 in Advanced Melanoma

This study is currently recruiting participants.
Verified February 2014 by Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb Identifier:
First received: June 14, 2012
Last updated: February 25, 2014
Last verified: February 2014

The purpose of this study is to evaluate pharmacodynamic changes of BMS-936558 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced).

Condition Intervention Phase
Advanced Melanoma
Metastatic Melanoma
Biological: BMS-936558 (Anti-PD-1)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Exploratory Study of the Biologic Effects of BMS-936558 (Anti-PD-1 Monoclonal Antibody) Treatment in Subjects With Advanced Melanoma (Unresectable or Metastatic)

Resource links provided by NLM:

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Pre-dose day 1 ] [ Designated as safety issue: No ]
  • Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Up to day 57 (Cycle 2 Day 1) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of BMS-936558 as measured by the incidence of adverse events (AEs), serious AEs, death, and changes in vital signs [ Time Frame: Up to 14 weeks after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of BMS-936558 as measured by laboratory test abnormalities [ Time Frame: Every 2 weeks up to 14 weeks after last treatment ] [ Designated as safety issue: Yes ]
  • Antitumor Activity of BMS-936558 as measured by the objective response rate (ORR), duration of response, and progression free survival (PFS) [ Time Frame: Every 8 weeks until confirmed disease progression and in follow-up if no progression ] [ Designated as safety issue: No ]
  • Immunogenicity of BMS-936558 as measured by the frequency of subjects with at least one positive ADA assessment and the frequency of subjects who develop anti-drug antibodies (ADA) after a negative baseline assessment [ Time Frame: Day 1, Day 15, Day 43 of cycle 1, Day 1 of cycle 2, Day 15 of cycle 3, every 16 weeks after cycle 3 Up to 2 years, and at Follow-up visits 1 (49±3 days after last treatment) and Follow-up visit 2 (90-120 days since last treatment) ] [ Designated as safety issue: Yes ]
  • Association between Programmed cell death ligand 1 (PD-L1) and clinical efficacy will be measured by PDL1 expression levels clinical activity (ORR, PFS) [ Time Frame: Pre-dose Up to Day 1 (screening) and Day 29 of cycle 1 ] [ Designated as safety issue: No ]
    Screening (day -7 to day 1 predose)

Estimated Enrollment: 160
Study Start Date: October 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: BMS-936558 (3 mg/kg) Biological: BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 3 mg/kg, Every 2 weeks, Up to 2 years depending on response


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

For more information regarding BMS clinical trial participation, please visit

Inclusion Criteria:

  • Men and women > 18 years
  • Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
  • Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
  • Subject must have histologic or cytologic confirmation of advanced melanoma
  • Subjects must have 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
  • Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

Exclusion Criteria:

  • Active or progressing brain metastases
  • Other concomitant malignancies (with some exceptions per protocol)
  • Active or history of autoimmune disease
  • Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
  • History of any hepatitis
  • Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy
  Contacts and Locations
Please refer to this study by its identifier: NCT01621490

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

United States, California
Local Institution Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Site 0015         
United States, Illinois
University Of Chicago Active, not recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins Active, not recruiting
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, Site 0010    617-632-5053      
Dana Farber Cancer Institute Active, not recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Ctr Recruiting
New York, New York, United States, 10065
Contact: Jedd Wolchok, Site 0009         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Walter J Urba, Site 0001         
United States, Tennessee
Vanderbilt-Ingram Cancer Ctr Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jeffrey Sosman, Site 0012         
United States, Texas
The University Of Texas Md Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Wen-Jen Hwu, Site 0006         
United States, Virginia
University Of Virginia Health System Active, not recruiting
Charlottesville, Virginia, United States, 22908
United States, Washington
Seattle Cancer Care Alliance Active, not recruiting
Seattle, Washington, United States, 98109
Local Institution Recruiting
Pamplona, Spain, 31192
Contact: Site 0008         
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb Identifier: NCT01621490     History of Changes
Other Study ID Numbers: CA209-038, 2012-001840-23
Study First Received: June 14, 2012
Last Updated: February 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions processed this record on April 21, 2014