Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma

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)

Detailed 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

Eligibility: 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

Relevance to patient case: possibly relevant