A phase Ia/Ib trial of trametinib in combination with sorafenib in patients with advanced hepatocellular cancer.

TPS469 Background: MEK inhibitorshave demonstrated preclinical activity in hepatocellular carcinoma (HCC). More importantly, in xenograft models, this class of inhibitors acts synergistically with sorafenibto inhibit tumor growth, prevent metastatic spread and increase survival. In preclinical models, sorafenibleads to overactivation of the MAPK pathway, which can be counterbalanced by the use of MEK inhibitors. Trametinibis a reversible, highly selective, allosteric MEK inhibitor. Methods: This is an open label, single group, phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary objective of this study is to determine maximally tolerated dose (MTD) of trametinibin combination with sorafenibas first-line systemic treatment for patients with locally advanced or metastatic HCC. Secondary objectives are to explore and characterize the safety and tolerability of this combination at the established MTD and to explore its efficacy profile. Up to 24 pati...