Phase I Trial Of Tivantinib In Combination With Carboplatin And Pemetrexed As First-Line Treatment In Patients With Advanced Nonsquamous Non Small Cell Lung Cancer Or Malignant Pleural Mesothelioma.

2549 Background: Tivantinib (T) is a selective non-ATP competitive oral inhibitor of MET receptor. Preclinical data showed that MET inhibition blocks Malignant Pleural Mesothelioma (MPM) and Non Small Cell Lung Cancer (NSCLC) cell growth and migration. Adding T to standard first-line chemotherapy may improve efficacy. Methods: Patients (pts) with advanced MPM or non-squamous NSCLC were eligible to receive escalating doses of T combined with carboplatin (C) AUC 5 i.v. d1-q21 and pemetrexed (P) 500 mg/m2 i.v. d1-q21 as first-line treatment. After 6 cycles of CP, T is continued as maintenance therapy until progression. Pts must be chemo-naive with ECOG Performance Status (PS) u003c 2 and adequate bone marrow, liver, and kidney functions. A standard 3+3 dose-escalation design was employed starting from dose level 0 (T 240 mg BID). The primary endpoint of the phase I study was to assess the maximum tolerated dose (MTD), defined as the highest dose level at which no more than 1 of 6 pts experiences a dose limiting ...