Combination of Regorafenib and Nivolumab in Unresectable Hepatocellular Carcinoma

Summary

Regorafenib and nivolumab are proven effective agents for the management of unresectable hepatocellular carcinoma patients. As preclinical studies have suggested potential synergism between antiangiogenic agents and immune checkpoint inhibitors, regorafenib and nivolumab may have synergism in terms of efficacy. Herein, this study investigates the combination of regorafenib and nivolumab as first-line therapy in patients with unresectable hepatocellular carcinoma.

Timeline

Start

2020-06-16

Primary completion

2022-05-30

Completion

2022-11-30

Outcome

Met primary endpoint

paper ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. PMID 38374347 ↗

Publications

• Background Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.
• Background Yoo C, Park JW, Kim YJ, Kim DY, Yu SJ, Lim TS, Lee SJ, Ryoo BY, Lim HY. Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma. Invest New Drugs. 2019 Jun;37(3):567-572. doi: 10.1007/s10637-018-0707-5. Epub 2018 Dec 7.
• Background Yoo C, Ryu YM, Kim SY, Kim J, Ock CY, Ryu MH, Kang YK. Association between the exposure to anti-angiogenic agents and tumour immune microenvironment in advanced gastrointestinal stromal tumours. Br J Cancer. 2019 Nov;121(10):819-826. doi: 10.1038/s41416-019-0596-1. Epub 2019 Oct 14.
• Background El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
• Kim HD, Jung S, Lim HY, Ryoo BY, Ryu MH, Chuah S, Chon HJ, Kang B, Hong JY, Lee HC, Moon DB, Kim KH, Kim TW, Tai D, Chew V, Lee JS, Finn RS, Koh JY, Yoo C. Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial. Nat Med. 2024 Mar;30(3):699-707. doi: 10.1038/s41591-024-02824-y. Epub 2024 Feb 19.

Drugs

Indications