744TiP - Met-Positive Advanced Hepatocellular Carcinoma and Child-Pugh Class a Liver Function in Asian Patients: a Randomized, Multicenter, Phase Ib/Ii Trial of the Oral C-Met Inhibitor Msc2156119J Vs Sorafenib

Abstract

ABSTRACT Background: Advanced hepatocellular carcinoma (HCC) is associated with a poor prognosis. Sorafenib is the recommended treatment for HCC patients (pts); however, it is not widely used in Asia due to affordability and unsatisfactory efficacy. The highly selective c-Met inhibitor MSC2156119J showed promising antitumor activity in a phase I trial (Falchook et al. J Clin Oncol 2013:31[Suppl]:2506) with a recommended phase II dose (RP2D) of 500 mg/d. This phase Ib/II, open-label, multicenter trial assesses the efficacy of MSC2156119J monotherapy in first-line treatment vs sorafenib in Met-positive (Met+) advanced HCC pts (NCT01988493). Trial design: Primary objectives include confirmation of the RP2D of 500 mg MSC2156119J in HCC pts (phase Ib) and evaluation of MSC2156119J monotherapy efficacy vs sorafenib, as determined by time to progression (TTP) per independent read (phase II). Secondary objectives are preliminary antitumor activity of MSC2156119J, pharmacokinetics (phase Ib), tolerability, safety, and antitumor activity of MSC2156119J vs sorafenib (phase II: overall survival, objective response, disease control, time to symptomatic progression, progression-free survival, and TTP per investigator read). Main eligibility criteria include: Asian adults with confirmed advanced HCC of BCLC Stage C, Child-Pugh Class A liver function, ECOG status 0–2 (only phase II: Met + , defined as moderate or strong protein overexpression determined by immunohistochemistry, measurable disease according to RECIST v1.1, and eligible for sorafenib treatment), life expectancy >3 mo, no prior systemic anticancer treatment or treatment targeting the HGF/c-Met pathway (phase II only), no neoplasm other than HCC, and no impaired cardiac function, history of liver transplant, or gastrointestinal disease. The Phase Ib part is a “3 + 3” dose-escalation design (300 or 500 mg MSC2156119J p.o./d; 21-d cycle) enrolling up to 18 pts. The phase II part is planned to randomize 140 pts (1:1) who receive MSC2156119J at the RP2D p.o./d or 400 mg sorafenib p.o./twice daily (21-d cycle). Enrollment began on Jan 9, 2014. Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting. All rights reserved. Disclosure: L. Xu: Employee of Merck Serono Pharmaceutical RD H. Zheng: Stock ownership: Merck/EMD Serono Employee of EMD Serono, Boston, MA; F. Bladt: Employee of Merck KGaA, Darmstadt, Germany. All other authors have declared no conflicts of interest.