PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
Condition: Advanced Melanoma; Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Nivolumab; Ipilimumab
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 227.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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)
    

Eligibility criteria:

        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