Hepatic Arterial Infusion Chemotherapy Plus Envafolimab and Lenvatinib for First-Line Unresectable Advanced Biliary Tract Cancer

Summary

Advanced biliary tract cancer has a poor prognosis and limited efficacy with current regimens. This multicenter single-arm phase Ib/II trial explores the efficacy and safety of HAI-GP chemotherapy combined with intraoperative arterial envafolimab and lenvatinib as first-line therapy for unresectable BTC. It conducts dose exploration to confirm the optimal dosage and evaluates clinical outcomes, aiming to establish a better comprehensive treatment strategy.

Timeline

Start

2026-06

Primary completion

2029-03

Completion

2029-12

Publications

• Background Jian Zhou FJ, Shi Guo-Ming, et al. . Gemox chemotherapy in combination with anti-PD1 antibody toripalimab and lenvatinib as first-line treatment for advanced intrahepatic cholangiocarcinoma: A phase 2 clinical trial. JOURNAL OF CLINICAL ONCOLOGY, 2021, 39(15_suppl):4094-4094 doi:10.1200/JCO.2021.39.15
• Background Victoria Ruiz I, Uboha NV, Jamal R, Mejia FC, Ahumada M, Im SA, Gomez-Roca C, Shapira-Frommer R, Perets R, Yanez E, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Castanon E. Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study. Clin Colorectal Cancer. 2026 Jun;25(2):225-238.e2. doi: 10.1016/j.clcc.2026.01.003. Epub 2026 Jan 22.
• Background Li J, Deng Y, Zhang W, Zhou AP, Guo W, Yang J, Yuan Y, Zhu L, Qin S, Xiang S, Lu H, Gong J, Xu T, Liu D, Shen L. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors. J Hematol Oncol. 2021 Jun 21;14(1):95. doi: 10.1186/s13045-021-01095-1.
• Background Macarulla T, Ren Z, Chon HJ, Park JO, Kim JW, Pressiani T, Li D, Zhukova L, Zhu AX, Chen MH, Hack SP, Wu S, Liu B, Guan X, Lu S, Wang Y, El-Khoueiry AB. Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial. J Clin Oncol. 2025 Feb 10;43(5):545-557. doi: 10.1200/JCO.24.00337. Epub 2024 Oct 18.
• Background Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.
• Background Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017 Sep;7(9):943-962. doi: 10.1158/2159-8290.CD-17-0245. Epub 2017 Aug 17.
• Background Chai Y. Immunotherapy of biliary tract cancer. Tumour Biol. 2016 Mar;37(3):2817-21. doi: 10.1007/s13277-015-4743-x. Epub 2016 Jan 4.
• Background Mu MY, Chen ZX, Cao YZ, Fu XB, Qiu LJ, Qi H, Gao F. Transarterial chemoembolization combined with intra-arterial infusion of sintilimab and bevacizumab for advanced hepatocellular carcinoma: a phase 2 study. Cancer Lett. 2025 Sep 28;628:217851. doi: 10.1016/j.canlet.2025.217851. Epub 2025 Jun 3.
• Background Shen L, Cao F, Liu Y, Nuerhashi G, Lin L, Tan H, Wen C, Wang Y, Chen S, Zou H, Xie L, Fan W. Hepatic artery infusion of FOLFOX chemotherapy plus camrelizumab combined with sorafenib for advanced hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (Double-IA-001): a phase II trial. BMC Med. 2025 May 9;23(1):275. doi: 10.1186/s12916-025-04110-1.
• Background Cai Z, He C, Zhao C, Lin X. Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma. Front Oncol. 2021 Apr 1;11:611118. doi: 10.3389/fonc.2021.611118. eCollection 2021.
• Background Cercek A, Boerner T, Tan BR, Chou JF, Gonen M, Boucher TM, Hauser HF, Do RKG, Lowery MA, Harding JJ, Varghese AM, Reidy-Lagunes D, Saltz L, Schultz N, Kingham TP, D'Angelica MI, DeMatteo RP, Drebin JA, Allen PJ, Balachandran VP, Lim KH, Sanchez-Vega F, Vachharajani N, Majella Doyle MB, Fields RC, Hawkins WG, Strasberg SM, Chapman WC, Diaz LA Jr, Kemeny NE, Jarnagin WR. Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):60-67. doi: 10.1001/jamaoncol.2019.3718.
• Background Huang XY, Shi GM, Zheng ZT, Sun HC, Liang F, Ji Y, Chen Y, Yang GH, Hu ZQ, Lu JC, Meng XL, Guo XJ, Zhang CC, Fan J, Zhou J. Anti-PD1 antibody toripalimab combined with lenvatinib, or GEMOX chemotherapy combined with lenvatinib as first-line therapy in patients with advanced intrahepatic cholangiocarcinoma: a randomized, open, two-cohort Phase 2 Study. BMC Med. 2025 Oct 21;23(1):573. doi: 10.1186/s12916-025-04404-4.
• Background Oh DY, He AR, Bouattour M, Okusaka T, Qin S, Chen LT, Kitano M, Lee CK, Kim JW, Chen MH, Suksombooncharoen T, Ikeda M, Lee MA, Chen JS, Potemski P, Burris HA 3rd, Ostwal V, Tanasanvimon S, Morizane C, Zaucha RE, McNamara MG, Avallone A, Cundom JE, Breder V, Tan B, Shimizu S, Tougeron D, Evesque L, Petrova M, Zhen DB, Gillmore R, Gupta VG, Dayyani F, Park JO, Buchschacher GL Jr, Rey F, Kim H, Wang J, Morgan C, Rokutanda N, Zotkiewicz M, Vogel A, Valle JW. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024 Aug;9(8):694-704. doi: 10.1016/S2468-1253(24)00095-5. Epub 2024 May 29.
• Background Eberlein TJ. Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer. Yearbook of Surgery 2011;2011(310-312, doi:10.1016/s0090-3671(10)79889-x
• Background Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet. 2005 Oct 8;366(9493):1303-14. doi: 10.1016/S0140-6736(05)67530-7.
• Background Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.
• Background Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
• Background Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol. 2014 Mar 7;6:99-109. doi: 10.2147/CLEP.S37357. eCollection 2014.
• Background Benavides M, Anton A, Gallego J, Gomez MA, Jimenez-Gordo A, La Casta A, Laquente B, Macarulla T, Rodriguez-Mowbray JR, Maurel J. Biliary tract cancers: SEOM clinical guidelines. Clin Transl Oncol. 2015 Dec;17(12):982-7. doi: 10.1007/s12094-015-1436-2. Epub 2015 Nov 25.

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