Phase 2, multicenter study of the EZH2 inhibitor tazemetostat as monotherapy in adults with relapsed or refractory (R/R) malignant mesothelioma (MM) with BAP1 inactivation.

8515Background: MM often presents at an advanced stage with a median survival of ~1 year. Treatments are limited; none clearly improve survival in second-line. In 40–60% of MM patients (pts) BRCA1 associated protein 1 (BAP1) is inactive and linked to a dependency on EZH2 (enhancer of zeste-homolog 2). EZH2 regulates gene expression to prevent differentiation of stem and progenitor cells, and aberrant EZH2 activity is implicated as an oncogenic driver. Tazemetostat, a potent, selective, oral EZH2 inhibitor demonstrated clinical activity in other malignancies; here we report preliminary data in inactive BAP1 MM. Methods: This is a phase 2, multicenter, open-label, single-arm study of tazemetostat (800 mg po BID) in pts with measurable R/R MM. PK and safety were assessed in a cohort of 13 pts. Efficacy was assessed via a 2-stage Green Dahlberg design in 61 pts with inactive BAP1 with a primary endpoint of 12-week disease control rate [DCR; CR or PR + SD]. Response was evaluated every 6 weeks with modified RE...