A phase I trial of binimetinib in combination with gemcitabine (G) and cisplatin (C) patients (pts) with untreated advanced biliary cancer (ABC)

e15125 Background: Activating mutations in the RAS/RAF/MEK/ERK signaling pathway are commonly found in ABC. Binimetinib is an oral, selective small molecule inhibitor of MEK1/2; single agent activity of Binimetinib in ABC has previously been observed. Preclinical data support anti-tumor synergy for Binimetinib when combined with G & C, administered in an interrupted dosing schedule. Methods: A Single arm, non-randomized, open-label, phase I,evaluated Binimetinib in combination with G and C in pts with untreated ABC, who had advanced measurable disease, ECOG 0-1, adequate bone marrow, renal, hepatic and cardiac function. The primary endpoint was to determine the MTD. Tumor tissue for targeted gene sequencing, blood samples for peripheral blood pERK expression and cell cycle analysis were evaluated. Patients received oral Binimetinib twice daily with G and C IV infusions day 8 and 15 of a 21 days cycle in a standard 3 + 3 dose escalation scheme. Binimetinib was held for 2 days prior to and on day of each G ...