Skip to Main content Skip to Navigation
Journal articles

Phase 1b/2 trial of tepotinib in sorafenibpretreated advanced hepatocellular carcinoma with MET overexpression

Abstract : Abstract Background This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenibpretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b (‘3 + 3’ design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2). Results In Phase 1b ( n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 ( n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5–74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%). Conclusions Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit–risk balance in sorafenibpretreated aHCC with MET overexpression. Trial Registration ClinicalTrials.gov: NCT02115373.
Document type :
Journal articles
Complete list of metadata

https://hal-univ-paris.archives-ouvertes.fr/hal-03244360
Contributor : Hal Paris Diderot <>
Submitted on : Tuesday, June 1, 2021 - 10:58:32 AM
Last modification on : Friday, June 4, 2021 - 11:24:03 AM

File

s41416-021-01334-9.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Thomas Decaens, Carlo Barone, Eric Assenat, Martin Wermke, Angelica Fasolo, et al.. Phase 1b/2 trial of tepotinib in sorafenibpretreated advanced hepatocellular carcinoma with MET overexpression. British Journal of Cancer, Cancer Research UK, 2021, ⟨10.1038/s41416-021-01334-9⟩. ⟨hal-03244360⟩

Share

Metrics

Record views

13

Files downloads

31