First-line tepotinib (MSC2156119J), an oral c-Met inhibitor, versus sorafenib i
PUBLISHED: 2015-11-27  702 total views, 2 today

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


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