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M. Kalevras



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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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      P3.04-013a - CONFIRM: A Phase III Randomized Trial to Evaluate the Efficacy of Nivolumab versus Placebo in Relapsed Mesothelioma (ID 8542)

      09:30 - 09:30  |  Author(s): M. Kalevras

      • Abstract
      • Slides

      Background:
      Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Despite a significant number of clinical studies in the second line setting, no randomized study has been positive. Early promising signals of activity relating to both PD-L1 and PD-1 targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint, and support the development of a randomized phase III trial to evaluate the efficacy of nivolumab. CONFIRM is the first ever placebo controlled, randomized phase III trial of a PD-1/PD-L1 immune checkpoint inhibitor in mesothelioma.

      Method:
      The primary objective is to determine whether nivolumab increases overall survival (OS) in relapsed mesothelioma. Secondary objectives are to determine whether nivolumab a) increases progression-free survival, b) increases response rate, c) has good safety/tolerability, and d) results in acceptable patient quality of life and cost per quality adjusted life year. A translational study will be undertaken to determine the correlation between OS and i) PD-L1 expression, ii) mutational burden (estimated by genome-wide analysis of copy number alterations), iii) immunotranscriptomic profile. Developed by researchers at the Universities of Leicester and Southampton on behalf of the UK NCRI Lung Clinical Studies Group the trial is co-ordinated by the Cancer Research UK Southampton Clinical Trials Unit in the UK, within the Centre of Cancer Immunotherapy. The trial will recruit 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy, from UK sites between March 2017 and 2021. We are also investigating opening recruitment to international sites. Patients will be randomized 2:1 (treatment: control), stratified according to epithelioid vs. non-epithelioid and center, to receive 240mg nivolumab (anti PD-1 antibody) monotherapy or saline placebo as a 30-minute intravenous infusion. Allocation will be double-blind. Treatment will be on day one of each 14-day cycle, until disease progression for a maximum of 12 months. Trial follow up will continue for 6 months after the last participant has progressed, or completed or discontinued treatment. The trial is powered (80%, with 2-sided 4% significance level) to detect a hazard ratio of 0.7 using an adjusted Cox regression model (time-to-event) and will be analyzed using intention-to-treat. This trial is funded by Cancer Research UK (C16728/A21400) and Bristol Myers Squibb (CA 209-841). Trial registrations: NCT03063450 and ISRCTN79814141.

      Result:
      Section not applicable

      Conclusion:
      Section not applicable

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