4283 - Phase 2 trial of tepotinib vs sorafenib in Asian patients (pts) with advanced hepatocellular carcinoma (HCC)

Background

MET is a potential therapeutic target in HCC. Tepotinib, a potent and highly selective MET inhibitor, has antitumor activity in pts with MET+ tumors. Phase 1b of the current trial (NCT01988493), confirmed the recommended phase 2 dose (RP2D) of tepotinib in Asian advanced HCC pts; here we describe phase 2 outcomes for tepotinib vs sorafenib.

Methods

Asian adults with MET + (2+ or 3+ by immunohistochemistry) advanced HCC (Barcelona clinic liver cancer Stage B/C; Child-Pugh Class A without encephalopathy; Eastern Cooperative Oncology Group performance status 0–1; no prior systemic advanced HCC therapy) were randomized (1:1) to tepotinib 500 mg once daily (RP2D) or sorafenib 400 mg twice daily in 21-day cycles. Endpoints: time to progression (TTP: primary endpoint), safety, progression-free survival (PFS), overall survival (OS) and tumor response. Efficacy was assessed by independent review committee (IRC) and investigators.

Results

Of 90 pts randomized, 75 were included in the efficacy analysis (tepotinib n = 38, sorafenib n = 37): median age 57 [range 31–78] years; 84.0% <65 years old; 94.7% male). TTP by IRC was statistically significantly longer for tepotinib vs sorafenib (2.8 vs 1.4 months; hazard ratio [HR] (90% confidence interval [CI]): 0.42 (0.26, 0.70); p = 0.0043). Median PFS by IRC was also statistically significantly longer for tepotinib (2.8 vs 1.4 months; HR (90% CI): 0.53 (0.33, 0.84); p = 0.0229). Median OS was similar between arms (tepotinib 9.3 vs sorafenib 8.6 months; HR [90%CI] 0.73 [0.43, 1.12]; p = 0.3039). Objective response rate by IRC was 10.5% (tepotinib) vs 0% (sorafenib) (p = 0.0438). There were 4 partial responses, all in the tepotinib arm. IRC outcomes were supported by investigator read data. In the safety analysis, treatment-related treatment-emergent adverse events (TRTEAEs) occurred in 37/45 (82%) and 43/44 (98%) pts and TRTEAEs grade ≥3 in 13/45 (29%) and 20/44 (46%) pts in the tepotinib and sorafenib arms, respectively. No new safety signals were noted.

Conclusions

Tepotinib provided significantly longer TTP and PFS than sorafenib in Asian pts with MET+ advanced HCC, with fewer reported overall and grade ≥3 TRTEAEs.

Clinical trial identification

NCT01988493.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

Medical writing assistance was provided by Helen Swainston PhD of Bioscript Science (Macclesfield, UK) and funded by Merck KGaA, Darmstadt, Germany.

Disclosure

J-W. Park: Honoraria: Bayer, BMS, Ono; Consulting and Advisory: BMS, Ono, Bayer, Eisai, Midatech, Roche; Corporate-sponsored research: BMS, Ono, Eisai, Bayer, Roche, Blueprint, AstraZeneca, Exelixis. D. Zhou: Employee: Merck Serono. J. Straub: Employee: Merck KGaA. C. Zhao: Employee: EMD Serono. All other authors have declared no conflicts of interest.