Overview

This trial is active, not recruiting.

Conditions advanced melanoma, metastatic melanoma
Treatments nivolumab, ipilimumab
Phase phase 1
Targets CTLA-4, PD-1
Sponsor Bristol-Myers Squibb
Start date September 2012
End date November 2017
Trial size 175 participants
Trial identifier NCT01621490, 2012-001840-23, CA209-038

Summary

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

United States California
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacodynamics study
Intervention model single group assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
Nivolumab 3 mg/kg solution intravenously Every 2 weeks, Up to 2 years depending on response
nivolumab BMS-936558 (MDX1106)
(Experimental)
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
nivolumab BMS-936558 (MDX1106)
ipilimumab BMS734016
(Experimental)
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
nivolumab BMS-936558 (MDX1106)
ipilimumab BMS734016
(Experimental)
Nivolumab 3 mg/kg solution intravenously as specified
nivolumab BMS-936558 (MDX1106)
(Experimental)
Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
nivolumab BMS-936558 (MDX1106)
ipilimumab BMS734016
(Experimental)
Nivolumab 3 mg/kg solution intravenously as specified
nivolumab BMS-936558 (MDX1106)

Primary Outcomes

Measure
Immunomodulatory effects of Nivolumab and Nivolumab in combination with Ipilimumab 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
Immunomodulatory effects of Nivolumab and Nivolumab in combination with Ipilimumab 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

Secondary Outcomes

Measure
Safety and tolerability of Nivolumab, Ipilimumab and Nivolumab in combination with Ipilimumab as measured by the incidence of adverse events (AEs), serious AEs, death, and changes in vital signs
time frame: Up to 100 days after last dose of study drug
Safety and tolerability of Nivolumab, Ipilimumab and Nivolumab in combination with Ipilimumab as measured by laboratory test abnormalities
time frame: Every 2 or 3 weeks up to 100 days after last treatment
Antitumor Activity of Nivolumab and Nivolumab in combination with Ipilimumab as measured by the objective response rate (ORR), duration of response, and progression free survival (PFS)
time frame: Approximately every 8 weeks until disease progression and in follow-up if no progression
Immunogenicity of Nivolumab and Nivolumab in combination with Ipilimumab as measured by the frequency of baseline positive subjects and the frequency of ADA positive subjects
time frame: Up to follow-up visit 2 (101-120 days since last treatment)
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: Part 1: Pre-dose up to Day 1 (screening Day -7 to day 1 predose) and Day 29 of cycle 1. Part 2, 3 and 4: Pre-dose (screening Day -28 to Day 1 predose) and week 2 or 4

Eligibility Criteria

Male or female participants at least 18 years old.

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Part 1: 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 Part 2, 3 and 4: Inclusion Criteria - Men and women >16 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 - Subjects must never received anti-CTLA4 therapy - Subjects must have histologic or cytologic confirmation of advanced melanoma - Subjects must have at least two measurable lesions at baseline by CT or MRI as per 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 - Subjects in Part 4 must have brain metastases Exclusion Criteria - Active or progressing brain metastases (except for Part 4 subjects) - Other concomitant malignancies (with some exceptions per protocol) - Active or history of autoimmune disease - Positive test for HIV 1&2 or known 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

Additional Information

Official title An Exploratory Study of the Biologic Effects of Nivolumab and Ipilimumab Monotherapy and Nivolumab in Combination With Ipilimumab Treatment in Subjects With Advanced Melanoma (Unresectable or Metastatic)
Description Allocation: Part 1 and 2: Single Arm study Part 3 and 4: Randomized Controlled Trial Intervention Model: Part 1 and 2: Single group: Single arm study Part 3 and 4: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study Minimum Age: Part 1: 18 Part 2, 3 and 4: 16
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Bristol-Myers Squibb.