A phase 2 randomized, double-blind, placebo-controlled study of tremelimumab for second and third line treatment in patients with unresectable pleural or peritoneal mesothelioma

Introduction Malignant mesothelioma (MM) is an uncommon cancer, caused principally by asbestos exposure. No treatments after first-line platinum-pemetrexed [1] have shown survival benefit [2], thus novel approaches are needed. Asbestos exposure induces immunosuppression and immune dysfunction in the mesothelium environment, mainly by hyperactivation of regulatory T lymphocytes and overproduction of cytokines that inhibit cytotoxic T lymphocytes and natural killer cells [3]. Cytotoxic T lymphocyteassociated antigen 4 (CTLA-4, CD152) modulates and eventually switches off T cell activation. Tremelimumab (treme) binds to the CTLA-4 antigen, preventing its negative regulatory signal to cytotoxic T cells. Results from a single arm phase 2 study of treme in 29 patients with MM who progressed on a platinum-based regimen showed promising 1and 2year survival rates and a safety profile consistent with previous treme studies [4]. This study has been expanded to enroll 29 patients currently treated with an optimized dosing schedule.