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A. Traynor



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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): A. Traynor

      • 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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    P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      P3.04-009 - Stereotactic Body Radiotherapy to All Sites of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Combined with Durvalumab and Tremelimumab (ID 10441)

      09:30 - 16:00  |  Author(s): A. Traynor

      • Abstract

      Background:
      PD-1/PD-L1 axis inhibition and comprehensive stereotactic body radiation (SBRT) treatment to all gross disease have both been independently associated with improved outcomes for patients with oligometastatic NSCLC in randomized trials. Interest has increased in the use of dual immune checkpoint inhibition in NSCLC, which adds targeting of CTLA-4 to PD-1/PD-L1 inhibition, as this has showed improved outcomes in melanoma, though with increased side effects. Recent appreciation for the immunostimulatory effects of SBRT and possible synergy with checkpoint inhibition therapies has prompted interest in combining these treatments, however the toxicity of this combination is unknown. This is the first trial evaluating the sequential combination of comprehensive SBRT and dual immune checkpoint inhibition.

      Method:
      This phase I trial will assess the safety and preliminary outcomes for a 21 patient cohort undergoing SBRT to all sites of oligometastatic (EGFR/ALK wildtype) NSCLC followed by combined duvalumab and tremelimumab immune checkpoint inhibition. Patients with 1-6 extracranial sites of disease will undergo SBRT from 30-50 Gy in 5 fractions. One week after radiation they will receive 4 cycles of combination Durvalumab 1500mg/Tremelimumab 75mg every 4 weeks followed by Durvalumab 1500mg monotherapy q 4 weeks. The primary endpoint of this study is safety. Secondary endpoints include overall survival (OS) and (PFS). Correlative studies of PD-L1 expression on post SBRT biopsy and circulating tumor cells are incorporated into the protocol.

      Result:
      Section not applicable

      Conclusion:
      The study is currently undergoing IRB review and FDA IND approval. This study will open to accrual in August 2017.