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Clinical Trial 19127

Cancer Type: Cutaneous
Interventions:BMS-936558 (Nivolumab); Ipilimumab; Nivolumab; Yervoy (Ipilimumab)

Study Type: Treatment
Phase of Study: Phase II

  • Zeynep Eroglu

Call 813-745-6100
or 1-800-679-0775

Study Title

A Study to Estimate the Anti-Tumor Activity and Identify Potential Predictors of Response in Patients with Advanced Mucosal or Acral Lentiginous Melanoma Receiving Standard Nivolumab in Combination with Ipilimumab Followed by Nivolumab Monotherapy


The purpose of this study is to determine which participants with melanoma respond best to nivolumab and ipilimumab treatment and to identify tumor and blood based markers that may predict response to the combination.


Primary Objective: 2.1 To assess objective response rate (ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria in patients with mucosal melanoma (MCM). Secondary Objectives: 2.2 To assess objective response rate (ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria in patients with acral lentiginous melanoma (ALM). 2.3 To determine progression-free survival (PFS), and overall survival (OS) in each cohort. 2.4 To determine whether pre-existing immune cells infiltrate, as well as Ki-67 and PDL1 expressing cells at the invasive tumor margin correlate with clinical response to a combination of CTLA-4 and PD-1 blocking therapy. 2.5 To evaluate subject¿s cancer genomic landscape using whole exome sequence profiling, identify the mutational pattern, and the frequency of somatic mutations and their relationship to tumor response in MCM and ALM, as well as subjects cancer genomic landscape using whole exome sequence profiling and utilize bioinformatic tools to translate mutations in exomes to identify specific driver mutations in MCM and ALM. Exploratory Objectives: 2.6 To evaluate tumors putative neoantigen epitopes from le exome sequencing data and determine binding affinity to MHC class I molecules as a potential predictor of response to combined checkpoint inhibitors treatment. 2.7 To determine clonal preservation, expansion, and selection of T-cell receptor rearrangement of tumor infiltrating lymphocytes before and after treatment with combined ipilimumab/nivolumab therapy as a correlative biomarker of treatment response. 2.8 To identify MCM and ALM gene expression profiling pattern associated with treatment response or resistance to combined checkpoint inhibitors treatment. 2.9 To identify relationship of specific gut microbiota in MCM and ALM with CD8+T cell function and anti-tumor immunity. 2.10 To identify circulating cell-free nucleic acids and its pattern that might be associated with combined checkpoint inhibitor treatment response/resistance in order to further narrow the application of combined checkpoint inhibitors to those who will benefit the most..

Inclusion Criteria

  • Participants must have histologically confirmed mucosal melanoma (MCM) or acral lentiginous melanoma (ALM) that is metastatic or unresectable.
  • Must be eligible to receive nivolumab in combination with ipilimumab treatment per institutional guidelines.
  • Must have a tissue block (or 20 unstained slides) available with adequate tumor to perform multiplex immunohistochemistry and nucleic acids analyses ( i.e., whole exome sequencing). Patients with only a previous fine-needle aspirate are ineligible for enrollment.
  • Must be willing to donate a small amount of whole blood prior to treatment and during treatment for laboratory analysis.
  • Must give informed consent prior to initiation of therapy.
  • Must be ambulatory with good performance status (ECOG 0 or 1).
  • Age 18 years or older.

  • Exclusion Criteria

  • Do not have available tissue for immunohistochemistry and nucleic acids analyses.
  • Have received prior immunotherapy for unresectable or metastatic disease.
  • Have untreated brain metastases, leptomeningeal disease, or seizure disorders. Patients with a history of brain metastases must have completed treatment (i.e., surgery or radiation) 1 month prior to enrollment and have no evidence of disease or edema on brain computed tomography (CT) or head magnetic resonance imaging (MRI).
  • Inadequate tissue for analysis.