745TiP - Phase Ib/Ii, Multicenter, Single-Arm Trial of the Oral C-Met Inhibitor Msc2156119J As Monotherapy in Patients with Met-Positive Advanced Hepatocellular Carcinoma with Child-Pugh Class a Liver Function Who Failed Sorafenib Treatment

Abstract

ABSTRACT Background: Sorafenib remains the only approved systemic first-line medical treatment for advanced hepatocellular carcinoma (HCC) patients (pts) with no validated option at the time of sorafenib failure. c-Met/hepatocyte growth factor (HGF) activation/overexpression is associated with poor prognosis. In a Phase I trial, the selective small-molecule c-Met inhibitor MSC2156119J displayed promising antitumor activity (Falchook et al. J Clin Oncol 2013). This disease-oriented Phase Ib/II, single-arm, multicenter study evaluates the safety and antitumor activity of MSC2156119J in Met-positive (Met+) advanced HCC pts with Child-Pugh Class A liver function, pretreated with sorafenib (EudraCT# 2013–002053–30). Trial design: Primary objectives are to determine the recommended Phase II dose of MSC2156119J (RP2D; Phase Ib) in HCC pts and to investigate antitumor activity by determining the progression-free survival (PFS) status at 12 wk per investigator read (Phase II). Secondary objectives include pharmacokinetics, antitumor activity (objective tumor response, time to progression, overall survival, PFS, and disease control), biochemical response, safety, and tolerability. European adults with confirmed, advanced HCC, Child-Pugh class A liver function, life expectancy >3 mo, ECOG status 0–1, available pretreatment tumor biopsy after sorafenib failure, pretreated with sorafenib for ≥4 wks and discontinued ≥14 days prior to day 1 of MSC2156119J treatment will be recruited. In the Phase II part, only Met+ pts with moderate or strong protein overexpression, as determined by immunohistochemistry, will be entered. Key exclusion criteria are prior treatment with systemic therapy other than sorafenib or with c-Met/HGF-targeting agents, impaired cardiac function, and chronic gastrointestinal disease. For the Phase Ib part, up to 18 pts are planned (3 + 3 design; 300 mg or 500 mg MSC2156119J p.o./day; 21-day cycle). For the Phase II part, 48 pts are planned to receive the RP2D of MSC2156119J (p.o./day; 21-day cycle), as determined in the Phase Ib part. Enrollment began on 06 May 2014. A Trial in Progress abstract was submitted to ASCO 2014. Disclosure: S. Faivre: Advisory board: Merck-Serono; B. Sarholz: Employee of Merck KGaA, Darmstadt, Germany A. Johne: Employee of Merck KGaA, Darmstadt, Germany; H. Zheng: Employee of EMD Serono, Boston, MA, USA Stock ownership: Merck/EMD Serono; E. Raymond: Advisory board: Merck-Serono