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M.J. Staab



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    MA 02 - Emerging Targets (ID 656)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      MA 02.01 - Evidence of Clinical Activity of Sitravatinib in Combination with Nivolumab in NSCLC Patients Progressing on Prior Checkpoint Inhibitors (ID 9720)

      11:00 - 12:30  |  Author(s): M.J. Staab

      • Abstract
      • Presentation
      • Slides

      Background:
      Combination therapy with agents that target the molecular and cellular mechanisms of resistance to checkpoint inhibitor therapy (CIT) is a rational approach to restoring or improving the efficacy of CIT in patients with immunotherapy resistant NSCLC. Sitravatinib is a spectrum-selective TKI which targets TAM receptors (Axl, MER), split family receptors (VEGFR2 and KIT), and MET. Inhibition of these target classes by sitravatinib may enhance anti-tumor activity through targeted depletion of immunosuppressive Type 2 tumor associated macrophages, regulatory T cells and myeloid-derived suppressor cells (MDSCs) and increasing antigen presentation capacity of dendritic cells in the tumor microenvironment (TME) thereby enhancing anti-tumor T effector and NK cell responses. Given these pleiotropic immune activating effects, the combination of sitravatinib with nivolumab is a rational approach to restoring or enhancing the clinical activity of CIT in patients with immunotherapy resistant NSCLC.

      Method:
      MRTX-500 is a Phase 2 Study of sitravatinib in combination with nivolumab in non-squamous NSCLC patients who have experienced progression of disease on or after treatment with CIT. The primary objective is to assess the clinical activity of the combination using ORR by RECIST 1.1. Enrollment into the Phase 2 treatment arm is stratified by prior outcome of CIT (e.g., clinical benefit versus progression of disease in ≤12 weeks). The investigational agent sitravatinib is administered orally in continuous regimen; nivolumab is administered intravenously, 240 mg every 2 weeks. The sample sizes for the treatment arms are based on two-stage Simon Optimal Design.

      Result:
      The recommended phase 2 dose of the combination is 120 mg of sitravatinib orally, once daily with nivolumab given at a flat dose of 240 mg IV Q 2 weeks. As of June 20, 2017, the study has enrolled 11 patients and 6/11 patients have had at least one on-study tumor assessment. Two patients out of 6 have achieved PR by RECIST. The first patient is a 72 yo female with pan-wild type metastatic NSCLC with history of treated brain metastases with multiple prior therapies who previously received pembrolizumab (stable disease for 14 months) and obtained confirmed PR at first disease evaluation. The second patient is a 71 yo female with pan-wild type metastatic NSCLC with multiple prior therapies who previously received nivolumab (progressive disease as best overall response) but who obtained unconfirmed PR at first disease evaluation. Treatment has been associated with manageable side effects to date.

      Conclusion:
      This study is ongoing and actively accruing patients.

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