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Charlotte Poille



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    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.06-02 - Mesothelioma Stratified Therapy (MiST): A Phase IIA Umbrella Trial for Accelerating the Development of Precision Medicines (ID 2465)

      10:15 - 18:15  |  Author(s): Charlotte Poille

      • Abstract

      Background

      There are currently no approved therapies for the treatment of relapsed mesothelioma. Recent advances in our understanding of inter-patient genomic heterogeneity, identification of potential drivers, and application of high throughput -omic technologies to clinical trial samples , has created opportunities to explore novel treatments in prospectively biomarker-enriched cohorts.

      Method

      MiST is a British Lung Foundation funded, University of Leicester sponsored multicentre national clinical trial. Patients (Pts) harbouring either pleural (any histological subtype) or peritoneal mesothelioma are eligible. Pts must have ECOG performance status 1 or 0, received prior standard chemotherapy and progressed from their last treatment (in any line). The study is designed in three stages. Stage 1 comprises prospective molecular profiling of the tumour suppressors BAP1, BRCA1, p16ink4A and the immune checkpoint inhibitor PDL1 (22C3), using automated immunohistochemistry. Stage 2: Patients meeting eligibility criteria are presently stratified into Arm 1: Rucaparib (PARP inhibitor) for BAP1 inactivated (cytoplasmic or loss of expression) /BRCA1 negative mesothelioma. Arm 2: Abemaciclib (CDK4/6 inhibitor) for p16ink4a negative tumour, Arm 3, Pembrolizumab (anti-PD1) and Bemcentinib (AXL) to patients without biomarker specification. Arm 4, Atezolizumab (anti-PDL1) and Avastin (anti-VEGF) for PDL1 positive MM. Further arms are in development. The primary endpoint is 12 week disease control (12wDCR), with the secondary endpoints, 24wDCR, response rate (modified RECIST1.1) and safety/tolerability. 12wDCR>50% will be considered worthy of further investigation. Stage 3: Genome wide somatic copy number analysis and transcriptomic analysis with in-silico deconvolution of immune cell infiltrates will be used to refine molecular correlates of response. Gut microbiome 16RNA sequencing will be conducted in arms 3 and 4. Patients exhibiting a response to treatment who then progress, will be re-biopsied to facilitate molecular interrogation of acquired resistance mechanisms. MiST is coupled to our laboratory functional genomics programme, aimed at exploring co-clinical trial models, to robustly define or validate mechanisms that underpin drug responses.

      Result

      Section not applicable

      Conclusion

      In summary, MiST is a new clinical research platform that will support proof-of-concept studies capable of testing biomarker enrichment/efficacy hypotheses, with the aim of advancing personalised therapy for mesothelioma.