Abstract 3990
Background
MET is a potential therapeutic target in advanced HCC; tepotinib is a highly selective MET inhibitor. Here we report final analysis results from a single-arm multicenter phase 2 study investigating the efficacy and safety of tepotinib in pts with sorafenib-treated advanced MET+ HCC (NCT02115373).
Methods
Adults with advanced MET+ HCC, Child-Pugh Class A, Eastern Cooperative Oncology Group performance status 0–1, and ≥4 weeks of prior sorafenib therapy were eligible for treatment. MET status was assessed by immunohistochemistry (2+ or 3+) and in-situ hybridization. Pts received tepotinib at the recommended phase 2 dose (RP2D) of 500 mg once-daily. The primary endpoint was progression-free survival status at 12 weeks; secondary endpoints included safety and other efficacy parameters.
Results
49 pts had received treatment; median (range) duration of therapy was 3.02 (0.03–16.49) months. Median (range) age was 66 (19–82) years and most patients were male (83.7%). The null hypothesis that the rate of progression-free subjects at 12 weeks is ≤ 15% has been rejected as 31/49 pts (63.3%; 90% confidence interval [CI]: 50.5, 74.7) were progression-free at 12 weeks; median PFS was 3.4 months (90% CI: 2.8, 4.2). Overall, there were 4/49 responders (8.2%; 90% CI: 2.8, 17.7; 1 complete and 3 partial responses). Median overall survival was 5.6 months (90% CI: 5.1, 8.2 months). The most common treatment-related adverse events (AEs) were peripheral edema (n = 32; 38.8%), fatigue (n = 10; 18.4%) and diarrhea (n = 16; 16.3%). 17 pts (34.7%) discontinued treatment due to AEs and 1 pt (2%) died from a treatment-related AE (hypoglycemic coma).
Conclusions
These data indicate that tepotinib has anti-tumor activity in pretreated MET+ advanced HCC and was well tolerated at the RP2D, with no new safety signals detected.
Clinical trial identification
NCT02115373.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany.
Editorial Acknowledgement
Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Martin Quinn, PhD of Bioscript Science (Macclesfield, UK).
Disclosure
C. Barone: Advisory board membership, Fee for presentation: Merck Serono. M. Wermke: Honaries: BMS, Novartis, Roche, Bayer, Glenmark, AstraZeneca; Travel reimbursements: AstraZeneca, BMS, MSD, Novartis, Glenmark; Research funding: Novartis, Pfizer. P. Merle: Advisory board member: Bayer, Ipsen, BMS. J.F. Blanc: Advisory board member: Bayer, Lilly Oncology, BMS, Onxeo, Esai, Ipsen. R. Bruns, J. Straub: Employee: Merck KGaA. C. Zhao: Employee: EMD Serono Inc. S. Faivre: Consultant, Clinical trials grants: Blueprint, BMS, Bayer Pharma, Eli Lilly, Ipsen, Merck Serono, MSD, Novartis. All other authors have declared no conflicts of interest.
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