Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression
Journal
British Journal of Cancer
Journal Volume
125
Journal Issue
2
Pages
200-208
Date Issued
2021
Author(s)
Ryoo B.-Y.
Ren Z.
Kim T.-Y.
Pan H.
Rau K.-M.
Choi H.J.
Park J.-W.
Kim J.H.
Yen C.J.
Lim H.Y.
Zhou D.
Straub J.
Scheele J.
Berghoff K.
Qin S.
Abstract
Background: This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods: In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). Results: In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26–0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ?3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. Conclusions: Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. Trial registration: ClinicalTrials.gov NCT01988493. ? 2021, The Author(s).
SDGs
Other Subjects
amylase; aspartate aminotransferase; bilirubin; creatinine; gamma glutamyltransferase; scatter factor receptor; sorafenib; tepotinib; triacylglycerol lipase; MET protein, human; piperidine derivative; pyridazine derivative; pyrimidine derivative; scatter factor receptor; sorafenib; tepotinib; advanced cancer; adverse drug reaction; aged; antineoplastic activity; Article; ascites; Asian; bacteremia; cancer growth; cancer patient; cancer survival; cancer therapy; clinical assessment; clinical evaluation; cohort analysis; controlled study; creatinine blood level; decreased appetite; dermatitis; diarrhea; disease control; drug dose escalation; drug safety; drug tolerability; drug withdrawal; fatigue; female; gene overexpression; hand foot syndrome; hepatic encephalopathy; human; hyperbilirubinemia; hypertension; hypertransaminasemia; hypoalbuminemia; liver cell carcinoma; liver failure; liver function; major clinical study; male; multicenter study; peripheral edema; phase 1 clinical trial; phase 2 clinical trial; progression free survival; QT prolongation; randomized controlled trial; time to progression; treatment indication; treatment response; upper gastrointestinal bleeding; adult; clinical trial; comparative study; drug administration; genetics; liver cell carcinoma; liver tumor; middle aged; oral drug administration; survival analysis; treatment outcome; upregulation; Administration, Oral; Adult; Aged; Asians; Carcinoma, Hepatocellular; Drug Administration Schedule; Female; Humans; Liver Neoplasms; Male; Middle Aged; Piperidines; Proto-Oncogene Proteins c-met; Pyridazines; Pyrimidines; Sorafenib; Survival Analysis; Treatment Outcome; Up-Regulation
Publisher
Springer Nature
Type
journal article