Clinical Trial: Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab in Melanoma Patients

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Feasibility Study to Identify the Optimal Adjuvant Combination Scheme of Ipilimumab and Nivolumab in Stage III Melanoma Patients

Brief Summary: This is a two-arm Phase 1b feasibility trial consisting of 20 patients receiving the combination of ipilimumab+nivolumab, either adjuvant, or split neo-adjuvant and adjuvant.

Detailed Summary:

Patients with stage III melanoma with palpable disease, naïve for CTLA-4/PD-1/PD-L1 immunotherapy, will be treated either post-surgery for 12 weeks with the combination of ipilimumab+nivolumab or in a split design for 6 weeks upfront surgery and for 6 weeks postsurgery. It is a two-arm Phase 1b feasibility trial consisting of 20 patients, 10 in each arm.

At different timepoints tumor biopsies and blood for PBMCs will be taken for translational research. Also scans will be done on specific timepoints.

The study will be held to determine safety, feasibility, and the immune-activating capacity of short-term combined neo-adjuvant and adjuvant ipilimumab + nivolumab. And to determine relapse free survival (RFS), any late adverse events, pharmacokinetics/pharmacodynamics, and the correlation between RFS and changes in neo-antigen specific T cell response.


Sponsor: The Netherlands Cancer Institute

Current Primary Outcome:

  • The alteration in magnitude of the neo-antigen specific T cell response in the time interval pre- to post-adjuvant therapy in peripheral blood [ Time Frame: 12 weeks from baseline ]
    To this purpose the immunogenic mutational load of each patient's melanoma will be determined by DNA and RNA sequencing from baseline biopsies (3x14g, 5ug tumor DNA). Proteasomal degradation and peptide presentation in HLA will be predicted in silico. MHC-tetramer staining containing the predicted peptides will be done as described before [2]. In addition, the effect of therapy on intratumoral T cell responses to obtain better insight into the mode of action of therapy will be analyzed. Identified neo-antigen specific T cells will be analyzed with respect to their phenotype and immunologic function (intracellular cytokine staining, lytic function as determined by CD107 staining, and coculture with APC presenting the cognate antigen).
  • Safety as measured by SUSARs. [ Time Frame: 12 weeks from baseline ]
  • The alteration in breadth of the neo-antigen specific T cell response in the time interval pre- to post-adjuvant therapy in peripheral blood [ Time Frame: 12 weeks from baseline ]
    To this purpose the immunogenic mutational load of each patient's melanoma will be determined by DNA and RNA sequencing from baseline biopsies (3x14g, 5ug tumor DNA). Proteasomal degradation and peptide presentation in HLA will be predicted in silico. MHC-tetramer staining containing the predicted peptides will be done as described before [2]. In addition, the effect of therapy on intratumoral T cell responses to obtain better insight into the mode of action of therapy will be analyzed. Identified neo-antigen spec

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Recurrence Free Survival, as determined according to RECIST 1.1 criteria. [ Time Frame: Until progression, median 10 months. ]
    • Rate of adverse events and late adverse events [ Time Frame: Until end of follow-up, median 3 years. ]
    • Type of adverse events and late adverse events [ Time Frame: Until end of follow-up, median 3 years. ]


    Original Secondary Outcome: Same as current

    Information By: The Netherlands Cancer Institute

    Dates:
    Date Received: April 13, 2015
    Date Started: April 2015
    Date Completion: April 2018
    Last Updated: October 3, 2016
    Last Verified: October 2016