Safety and efficacy of first-line tepotinib (MSC2156119J) in a phase Ib trial
PUBLISHED: 2015-11-27  858 total views, 2 today

Shukui Qin1, Ho yeong Lim2, Baek-yeol Ryoo3, Cindy Li4, Huiling Xiong4, Christian Ihling5, 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

 

Objective:The overall prognosis of advanced hepatocellular cancer (HCC) remains poor, with c-Met abnormalities associated with a particularly poor prognosis. The highly selective c-Met inhibitor tepotinib (MSC2156119J) demonstrated promising antitumor activity in a phase I trial. The results of the phase Ib part of a phase Ib/II trial of tepotinib as first-line therapy for Asian patients (pts) with advanced HCC (NCT01988493) are reported. Method: Adults with confirmed, advanced HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG status 0–2 were eligible for this open-label, single-arm, 3+3 dose-escalation study (tepotinib 300 or 500 mg p.o./day; 21-day cycle). Twelve pts were planned to be enrolled at the RP2D (total enrolment of up to 18 pts). c-Met status was determined at study entry, although Met+ status (c-Met protein overexpression of 2+/3+ on immunohistochemistry) was not required for eligibility for the phase Ib trial. Result: 20 pts were enrolled (median age, 57 [38-69] years; ECOG PS 0/1, 9/11; prior sorafenib, 19); 6 received tepotinib 300 mg/day and 14 received tepotinib 500 mg/day. At data cut-off, 16 patients had discontinued therapy, 14 due to disease progression. No dose-limiting toxicities were observed with either dose of tepotinib. 15 pts had tepotinib-related adverse events. The majority were grade 1/2 in severity; nine grade 3/4 events were observed, with three instances of grade 3 increased lipase levels. 6 of 15 pts with c-Met-negative disease had a best overall response (BOR) of stable disease (SD); BOR in the other 9 pts was progressive disease (PD). Of 3 pts with c-Met-positive disease, 1 had a partial response (PR), 1 SD, and 1 PD; all were treated with tepotinib 500 mg/day. BOR in the other 2 pts was PD (c-Met status indeterminate) and SD (c-Met status missing). Conclusion:Phase Ib data show that tepotinib at a dose up to 500 mg/day is well tolerated by Asian pts with advanced HCC. A PR was observed in a pt with a c-Met-positive tumor. Enrolment to the phase II part of the trial, in which pts with c-Met-positive tumors will be randomized to receive tepotinib 500 mg/day or sorafenib 400 mg twice-daily, is ongoing.

 

Key Words: hepatocellular cancer


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