PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma (PD-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01621490
First received: June 14, 2012
Last updated: August 4, 2014
Last verified: August 2014

June 14, 2012
August 4, 2014
September 2012
August 2017   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
  • 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 ] [ 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: 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 ]
Complete list of historical versions of study NCT01621490 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

    Time Frame:

    Part 1: 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, follow-up visit 1 (40-60 days after last treatment), and follow-up visit 2 (101-120 days since last treatment)

    Part 2, 3 and 4: Weeks 1, 3, 4, 7, 9, 10, 13, 25, 53, 79, 95 follow-up visit 1 (40-60 days after last treatment), and 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 ] [ Designated as safety issue: No ]
  • 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)
Not Provided
Not Provided
 
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
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)

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)

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

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Advanced Melanoma
  • Metastatic Melanoma
  • Biological: Nivolumab
    Other Name: BMS-936558 (MDX1106)
  • Drug: Ipilimumab
    Other Names:
    • BMS734016
    • Yervoy
  • Experimental: Part 1-Cohort 1 and 2: Nivolumab
    Nivolumab 3 mg/kg solution intravenously Every 2 weeks, Up to 2 years depending on response
    Intervention: Biological: Nivolumab
  • Experimental: Part 2-Arm A: Nivolumab + Ipilimumab
    Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
    Interventions:
    • Biological: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Part 3-Arm A: Nivolumab + Ipilimumab
    Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
    Interventions:
    • Biological: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Part 3-Arm B: Nivolumab
    Nivolumab 3 mg/kg solution intravenously as specified
    Intervention: Biological: Nivolumab
  • Experimental: Part 3-Arm C: Ipilimumab
    Ipilimumab 3 mg/kg solution intravenously as specified
    Intervention: Drug: Ipilimumab
  • Experimental: Part 4-Arm D: Nivolumab + Ipilimumab
    Nivolumab 1 mg/kg combined with Ipilimumab 3 mg/kg solution intravenously and then Nivolumab 3 mg/kg solution intravenously as specified
    Interventions:
    • Biological: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Part 4-Arm E: Nivolumab
    Nivolumab 3 mg/kg solution intravenously as specified
    Intervention: Biological: Nivolumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
August 2017
August 2017   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.
United States,   Netherlands,   Spain
 
NCT01621490
CA209-038, 2012-001840-23
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP