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  P2.06 - Poster Session with Presenters Present (ID 467)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17850

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    P2.06-008 - Phase 1/2 Study of Mocetinostat and Durvalumab (MEDI4736) in Patients with Advanced Solid Tumors and Non Small Cell Lung Cancer (NSCLC) (ID 5521)

    14:30 - 14:30  |  Author(s): M. Haigentz
    • Abstract
    • Slides

    Background:
    Immune checkpoint inhibitors produce durable clinical responses in a subset of patients, however strategies are needed to improve clinical efficacy of these agents and overcome innate or acquired resistance to therapy. Growing evidence suggests that tumors evade immune detection through modulation of intrinsic immunogenicity and inhibition of both innate and adaptive anti-tumor immune responses. Mocetinostat, a class I histone deacetylase inhibitor, has multiple potential immunomodulatory features including: 1) induction of tumor associated antigens and major histocompatibility complex Class I and Class II expression on tumor cells, 2) induction of immunogenic cell death via activation and cross-presentation of tumor antigens by antigen presenting cells, 3) enhanced function of T effector cells, and 4) decreased function of immunosuppressive cell subsets including regulatory T cells and myeloid derived suppressor cells. Given these pleiotropic immune activating effects, combination therapy of mocetinostat and PD-L1 blocking mAb, durvalumab, is a rational approach to restoring or enhancing the clinical activity of immune checkpoint blockade in patients with NSCLC.
    
    Methods:
    This open-label Phase 1/2 study is evaluating the tolerability and clinical activity of mocetinostat in combination with durvalumab. Secondary objectives include pharmacokinetics, incidence of anti-drug antibodies, and changes in tumor PD-L1 expression. Exploratory objectives evaluate changes in circulating and tumor cell PD-L1, circulating and tumor infiltrating immune cell populations and cytokines. Phase 1 explores increasing doses of mocetinostat administered orally (50, 70, 90 mg three times weekly [TIW]) in combination with durvalumab in patients with advanced solid tumors. The regimen begins with a 7-Day Lead-in Period of mocetinostat single agent TIW followed by the combination regimen with durvalumab (1500 mg intravenously every 28 days). Phase 2 evaluates the clinical activity of mocetinostat and durvalumab, as assessed by Objective Response Rate (ORR) by RECIST 1.1., in patients with NSCLC who have previously received at least one platinum containing doublet chemotherapy regimen for advanced disease. Four population cohorts are included: 1) immunotherapy naïve, no/low PD-L1 expression, 2) immunotherapy naïve, high PD-L1 expression, 3) prior clinical benefit with PD-L1 or PD-1 inhibitor treatment followed by progression, 4) prior treatment with PD-L1 or PD-1 inhibitor with progression within 16 weeks of initiation of treatment. Tumor PD-L1 expression will be determined by the SP263 assay. The sample sizes for the populations are based on two-stage Simon Optimal Designs. Status: Enrollment into the study opened in June 2016. Clinical Trial Information: NCT02805660
    
    Results:
    Section not applicable
    
    Conclusion:
    Section not applicable
    
    

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