Therapeutic outcomes for patients (pts) with advanced hepatocellular carcinoma (HCC) are currently poor, despite the introduction of new therapies. c-Met is a potential therapeutic target in HCC, and c-Met inhibitors have demonstrated activity in preclinical HCC models. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor that has favorable safety and promising clinical activity, particularly against c-Met+ solid tumors. We report the final results of a phase Ib trial of tepotinib in pts with advanced HCC.
Enrolled pts were Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2. Pts received tepotinib 300, 500 (the RP2D), or 1,000 mg/day on a 21-day cycle. c-Met expression was retrospectively determined by IHC (c-Met+ defined as ≥ 50% tumor IHC2+/3+). The primary objective was to confirm the recommended phase II dose (RP2D) of tepotinib.
No dose-limiting toxicities were observed in the 27 pts enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/16), who received tepotinib 300 mg/day (n = 7), 500 mg/day (n = 14), or 1,000 mg/day (n = 6, 3 with dose reduction). 22 pts had treatment-related treatment-emergent adverse events (TRTEAEs), most commonly diarrhea (n = 10), nausea (n = 8), elevated AST (n = 7), and elevated ALT (n = 6). The most common grade ≥3 TRTEAEs were elevated AST (n = 3), elevated ALT (n = 3), and elevated lipase (n = 3). Best overall response (BOR) was partial response (PR) in 2 pts, of duration 19.0 months (500 mg) and 4.4 months (1,000 mg). 8 pts had a BOR of stable disease (SD), 14 pts had PD, 1pt had Non-CR/Non-PD, 2pts were not evaluable. 5 pts had progression-free survival >8 months. Tumor c-Met status was available for 26 pts; of 7 pts with c-Met+ tumors, 2 had a PR and 2 had SD. PK and exploratory biomarkers were investigated.
Tepotinib had antitumor activity in Asian pts with advanced HCC, particularly those with c-Met+ tumors, and was well tolerated at doses up to 1,000 mg/day. A maximum tolerated dose was not defined. The efficacy and safety of first-line tepotinib in pts with c-Met+ HCC are being compared with those of sorafenib in the phase II part of this study.
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D. Zhou, C. Zhao, A. Becker: Employee of Merck. All other authors have declared no conflicts of interest.