Shukui Qin¹, Ho yeong Lim², Baek-yeol Ryoo³, Cindy Li⁴, Huiling Xiong⁴, Andreas Johne⁵, Ann-lii Cheng⁶

¹Medical Oncology Department, Nanjing Bayi Hospital, Nanjing, China, ²department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, ³Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, ⁴Merck Serono Pharmaceutical R&D Co., Ltd., Beijing, China, ⁵Merck KGaA, Darmstadt, Germany, ⁶Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

Background:HCC, a poor-prognosis disease for which the only approved drug is sorafenib, has a high unmet need. Factors associated with tumor aggressiveness in advanced HCC include c-Met amplification/over expression. The highly selective c-Met inhibitor tepotinib (MSC2156119J) has demonstrated antitumor activity in phase I trials in patients with solid tumors, particularly those with c-Met-positive disease. A maximum-tolerated dose of tepotinib has not been established at doses up to 1,400 mg/day, and a dose of 500 mg/day has been shown to inhibit c-Met activity by >95% in >90% of patients. Tepotinib was shown to be well tolerated in the phase IB part of this trial. Tepotinib 500 mg/day is being compared with sorafenib as first-line therapy for advanced HCC in the recently initiated phase II part of the trial (NCT01988493). Trial design: Adults with histologically/cytologically confirmed, measurable advanced HCC of Barcelona Clinic Liver Cancer Stage C are eligible for the randomized, open-label phase II trial, which will be conducted at 30–35 sites in China, South Korea, Taiwan, and other Asian countries. Eligible patients are also required to have Child-Pugh Class A liver function and ECOG performance status 0–2. Prior systemic therapy for HCC is not allowed. All patients must have c-Met-positive tumors, defined as c-Met protein overexpression (moderate [2+] or strong [3+] staining for c-Met in ≥50% of tumor cells using immunohistochemistry). A planned 140 patients will be randomized to receive first-line tepotinib 500 mg/day or sorafenib 400 mg BID over a 21-day cycle. The primary objective is to evaluate efficacy as measured by time to progression (TTP) of first-line single-agent tepotinib versus sorafenib. Secondary objectives are to evaluate the safety and tolerability as well as the antitumor efficacy of single-agent tepotinib versus sorafenib. Exploratory objectives include patient-reported outcomes and analysis of potential biomarkers. This large randomized phase II trial will provide evidence of whether tepotinib represents an effective alternative to sorafenib for the first-line treatment of Asian patients with c-Met-positive advanced HCC.

Key Words: HCC