Author of

• 30943

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30953

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    P2.04-12 - Ph I Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and SBRT to Multiple Sites in Patients with Stage IV NSCLC  (ID 2903)

    10:15 - 18:15  |  Author(s): Michael Jelinek
    • Abstract

    Background
    

    Despite the promise of immunotherapy for the treatment of advanced NSCLC, only a fraction of patients experience significant benefit from immunotherapy alone. Previous studies have shown that SBRT can stimulate innate and adaptive immunity to potentially augment immunotherapy. In addition, SBRT is used in patients with limited metastatic disease as consolidative approach, showing an improvement overall survival when compared to systemic treatment alone. Combining immunotherapy with ablative therapy is being studied by a number of investigators. While many of these pre-clinical and clinical studies are promising, timing of immunotherapy with SBRT has not be formally studied. Further, few of these studies have addressed treatment of multiple sites of disease and little is known about what molecular changes occur in the tumor microenvironment immediately after ablative therapy. This trial is designed to evaluate the safety and efficacy of the combination of nivolumab (N) and ipilimumab (I) plus sequential(S) or concurrent(C) SBRT in patients with stage IV NSCLC.

    Method
    

    This is a single-center phase I, open-label, two-arm, randomized platform trial. Eligible patients include those with stage IV NSCLC with >2 metastatic lesions that meet criteria for SBRT (0.2 cc to 65 cc of viable tumor, larger tumors able to be partially treated up to 65 cc). Eligible patients are simultaneously accrued on arm I (S) and arm II (C) in a 1:1 ratio. Participants in arm I complete SBRT to 2-4 sites followed by initiation of N/I 1-7 days after completion of SBRT. Participants in arm II are treated with N/I within 24-48 hours of SBRT with required SBRT completion to 2-4 sites within two weeks (prior to the second dose of N). Protocol therapy consists of treatment with N 3mg/kg every 2 weeks and I 1mg/kg every 6 weeks for a maximum of 24 months. The primary endpoint is dose-limiting toxicity defined as a >33% rate of grade ≥3 toxicity. DLT is defined as any grade ≥3 toxicity possibly, likely, or definitely related to SBRT plus N/I (the combination and not the individual components). 
Secondary endpoints include response rate and progression free survival at 6 months, control rate of treated lesions and non-treated lesions, and comparison of efficacy and toxicity between the arms. Biopsies and blood draws performed pre- and post-SBRT will facilitate molecular correlative studies including investigation of changes in the immune microenvironment induced by the two approaches.

    Result
    

    Current enrollment includes 27 of the 40-80 participants: 15 patients are enrolled on arm 1 (sequential) and 12 patients are enrolled on arm 2 (concurrent). SBRT safety cohorts, to which patients can contribute to more than one, include the following: central lung (n=20), peripheral lung (n=7), abdominal (n=5), osseous (n=9), and liver (n=5). All patients have paired pretreatment and posttreatment biopsies of at least one irradiated lesion. 79% of post-ablative biopsies are suitable for DNA/RNA sequencing.

    Conclusion
    

    Section not applicable