A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma

Summary

This clinical trial was designed to evaluate the safety and efficacy of Y90-SIRT combined with nivolumab, ipilimumab, and lenvatinib in patients with unresectable HCC. In addition to assessing short-term efficacy endpoints, such as ORR and PFS, this trial places particular emphasis on the OS benefit for patients. This study is therefore both novel and innovative.

Timeline

Start

2026-02

Primary completion

2026-06-30

Completion

2028-06-30

Publications

• Background Zhu HD, Fan WJ, Zhao C, Wang S, Li YL, Jin ZC, Zhang ZW, Guo JH, Cheng HT, Zhang Q, Lu J, Zeng YY, Lv WF, Xu H, Shao HB, Xu WG, Zhao XY, Gu SZ, Lin HL, Zheng WH, Piao LZ, Song YS, Zhao JB, Wang YC, Hou ZG, Sun Y, Guan N, Huang M, Yang WZ, Ji JS, Teng GJ. Transarterial Chemoembolization Combined With Camrelizumab and Rivoceranib for Unresectable Hepatocellular Carcinoma (CHANCE2005/CARES-005): A Randomized Phase II Trial. J Clin Oncol. 2026 Apr 10;44(11):959-969. doi: 10.1200/JCO-25-01796. Epub 2026 Feb 24.
• Background Feng Y, Roy A, Masson E, Chen TT, Humphrey R, Weber JS. Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma. Clin Cancer Res. 2013 Jul 15;19(14):3977-86. doi: 10.1158/1078-0432.CCR-12-3243. Epub 2013 Jun 5.
• Background Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.
• Background Kudo et al. HCC. Study 117. Phase 1b of lenvatinib + NIVO in unresectable HCC. ASCOGI 2020. Poster
• Background Agrawal et al. Journal for ImmunoTherapy of Cancer (2016) 4:72
• Background Zhan C, Ruohoniemi D, Shanbhogue KP, Wei J, Welling TH, Gu P, Park JS, Dagher NN, Taslakian B, Hickey RM. Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma. J Vasc Interv Radiol. 2020 Jan;31(1):25-34. doi: 10.1016/j.jvir.2019.05.023. Epub 2019 Aug 14.
• Background Mejait A, Roux C, Soret M, Larrey E, Wagner M, Bijot JC, Lussey-Lepoutre C, Thabut D, Goumard C, Maksud P, Allaire M. Enhanced therapeutic outcomes with atezolizumab-bevacizumab and SIRT combination compared to SIRT alone in unresectable HCC: A promising approach for improved survival. Clin Res Hepatol Gastroenterol. 2024 Feb;48(2):102282. doi: 10.1016/j.clinre.2024.102282. Epub 2024 Jan 6.
• Background DiFederico,A.,Rizzo,A.,Carloni,R.,DeGiglio,A.,Bruno,R.,Ricci,D.,&Brandi,G.(2022).Atezolizumab-bevacizumabplusY-90TAREforthetreatmentofhepatocellularcarcinoma:preclinicalrationaleandongoingclinicaltrials.Expertopiniononinvestigationaldrugs,
• Background Craciun L, de Wind R, Demetter P, Lucidi V, Bohlok A, Michiels S, Bouazza F, Vouche M, Tancredi I, Verset G, Garaud S, Naveaux C, Galdon MG, Gallo KW, Hendlisz A, Derijckere ID, Flamen P, Larsimont D, Donckier V. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer. 2020 Feb 19;20(1):135. doi: 10.1186/s12885-020-6613-1.
• Background Grass GD, Krishna N, Kim S. The immune mechanisms of abscopal effect in radiation therapy. Curr Probl Cancer. 2016 Jan-Feb;40(1):10-24. doi: 10.1016/j.currproblcancer.2015.10.003. Epub 2015 Nov 21.
• Background Formenti SC, Rudqvist NP, Golden E, Cooper B, Wennerberg E, Lhuillier C, Vanpouille-Box C, Friedman K, Ferrari de Andrade L, Wucherpfennig KW, Heguy A, Imai N, Gnjatic S, Emerson RO, Zhou XK, Zhang T, Chachoua A, Demaria S. Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med. 2018 Dec;24(12):1845-1851. doi: 10.1038/s41591-018-0232-2. Epub 2018 Nov 5.
• Background Jia Fan 2025 ESMO poster 1495
• Background Yau T, Galle PR, Decaens T, Sangro B, Qin S, da Fonseca LG, Karachiwala H, Blanc JF, Park JW, Gane E, Pinter M, Pena AM, Ikeda M, Tai D, Santoro A, Pizarro G, Chiu CF, Schenker M, He A, Chon HJ, Wojcik-Tomaszewska J, Verset G, Wang QQ, Stromko C, Neely J, Singh P, Jimenez Exposito MJ, Kudo M; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025 May 24;405(10492):1851-1864. doi: 10.1016/S0140-6736(25)00403-9. Epub 2025 May 8.
• Background Lu W, Zhang T, Xia F, Huang X, Gao F. Transarterial radioembolization versus chemoembolization for hepatocellular carcinoma: a meta-analysis. Front Oncol. 2025 Jan 17;14:1511210. doi: 10.3389/fonc.2024.1511210. eCollection 2024.
• Background 中国医师协会介入医师分会临床诊疗指南专委会, 中国研究型医院学会肝胆胰外科专业委员会. 钇-90微球选择性内放射治疗肝脏恶性肿瘤规范化操作专家共识（2024版）[J] . 中华医学杂志, 2024, 104(7) : 486-498.
• Background Kudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim JH, Zhao H, Li C, Madoff DC, Ghobrial RM, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry AB, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS, Llovet JM; LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025 Jan 18;405(10474):203-215. doi: 10.1016/S0140-6736(24)02575-3. Epub 2025 Jan 8.
• Background Sangro B, Kudo M, Erinjeri JP, Qin S, Ren Z, Chan SL, Arai Y, Heo J, Mai A, Escobar J, Lopez Chuken YA, Yoon JH, Tak WY, Breder VV, Suttichaimongkol T, Bouattour M, Lin SM, Peron JM, Nguyen QT, Yan L, Chiu CF, Santos FA, Veluvolu A, Thungappa SC, Matos M, Zotkiewicz M, Udoye SI, Kurland JF, Cohen GJ, Lencioni R; EMERALD-1 Investigators. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2025 Jan 18;405(10474):216-232. doi: 10.1016/S0140-6736(24)02551-0. Epub 2025 Jan 8.

Drugs

Indications