A Phase II Study of Toripalimab in Combination with Gemcitabine and 5-Fluorouracil as First-Line Therapy for Advanced or Metastatic Biliary Tract Carcinoma

Sep 30, 2026

Background/Objectives: Toripalimab plus biweekly 5-fluorouracil (5-FU) with gemcitabine has limited clinical evidence in first-line advanced biliary tract carcinoma (BTC), and predictive biomarkers of benefit remain unclear. Methods: This prospective phase II study enrolled unresectable or metastatic BTC patients receiving toripalimab with gemcitabine and biweekly 5-FU; primary endpoints were PFS and ORR, with OS and safety as secondary endpoints and exploratory PD-L1/TMB analyses. Results: 30 patients were enrolled; ORR was 13.0%, median PFS 5.3 months and OS 11.7 months. Subgroups by PD-L1 and TMB showed no significant PFS improvement. TRAEs occurred in all patients; grade 3–4 events occurred in 26.7% with no grade 5 AEs, and the safety profile was manageable. Conclusions: The regimen showed promising efficacy and tolerability as first-line therapy, but biomarkers require validation in larger studies.

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Article A Phase II Study of Toripalimab in Combination with Gemcitabine and 5-Fluorouracil as First-Line Therapy for Advanced or Metastatic Biliary Tract Carcinoma Fangyong Lei *, Wenjing Deng, Ying Zhou, Lilan Fang, Xiuxin Lin, Lingyu Qin, Chunming Li, Jian Rao and Gengsheng Yu * Received: 8 October 2025 Revised: 4 December 2025 Accepted: 26 December 2025 Published: 27 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Department of Oncology, Jiangmen Central Hospital, Jiangmen 529000, China; [wjdeng2011@163.com](wjdeng2011@163.com) (W.D.); [zhou21341215@126.com](zhou21341215@126.com) (Y.Z.); [fangli416@163.com](fangli416@163.com) (L.F.); [13822348180@163.com](13822348180@163.com) (X.L.); [qinlingyu007@163.com](qinlingyu007@163.com) (L.Q.); [sumsming@163.com](sumsming@163.com) (C.L.); [13500288552@163.com](13500288552@163.com) (J.R.) * Correspondence: [leify31039@yeah.net](leify31039@yeah.net) (F.L.); [gengsheng_yu@hotmail.com](gengsheng_yu@hotmail.com) (G.Y.) Simple Summary Biliary tract carcinoma (BTC) is a rare, aggressive cancer arising from biliary epithelial cells, often diagnosed at advanced stages with a median survival of less than one year. Prior investigations have explored the efficacy of programmed cell death protein 1 (PD-1) inhibitors and gemcitabine-based chemotherapy regimens in advanced BTC. In this phase II study, we evaluated a new regimen for advanced or metastatic BTC using toripalimab combined with gemcitabine and 5-fluorouracil (5-FU) . The regimen achieved an objective response rate (ORR) of 13% . Subgroup analyses revealed no significant improvement in outcomes among patients with elevated programmed death-ligand 1 (PD-L1) expression or high tumor mutational burden (TMB) . Treatment-related adverse events (TRAEs) occurred in all patients, with grade 3 or higher TRAEs reported in eight patients, including anemia (20%), neutropenia (13.3%), and nausea (6.6%); no treatment-related deaths were observed. Overall, this combination therapy offers a viable alternative for patients with advanced BTC and demonstrates an acceptable safety profile. Abstract Background/Objectives: The anti-PD-L1 antibody has been applied for use in first-line advanced biliary duct cancer patients. However, clinical evidence of toripalimab in combination with biweekly 5-fluorouracil (5-FU) is limited and predictive biomarkers of treatment benefits remain unclear. Methods: This prospective study enrolled patients with unresectable or metastatic BTC who received toripalimab in combination with gemcitabine and biweekly 5-FU. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). Secondary endpoints included overall survival (OS) and safety. Exploratory analyses evaluated associations between programmed cell death-ligand 1 (PD-L1) expression or tumor mutational burden (TMB) and clinical outcomes. Results: A total of 30 patients were enrolled, with a median follow-up duration of 16.0 months. The ORR was 13.0% . The median PFS and OS were 5.3 months (95% CI: 3.59–7.01) and 11.7 months (95% CI: 6.07–17.33), respectively. Subgroup analyses revealed no significant association between PD-L1 status or TMB level and improved PFS. All patients experienced adverse events (AEs), while grade 3–4 AEs occurred in eight patients (26.7%), most commonly anemia (20.0%), leukocytopenia (13.3%), and nausea (6.6%) . No grade 5 AEs were observed, and the safety profile was considered manageable. Conclusions: Toripalimab in combination with gemcitabine and 5-fluorouracil showed promising efficacy and was well-tolerated asa first-line therapy in advanced biliary duct cancer patients. Although PD-L1 expression and TMB did not predict treatment benefit, larger studies are needed to validate potential biomarkers and further opt

FAQs

What was the main purpose of this phase II study?

To evaluate toripalimab combined with gemcitabine and biweekly 5-FU as first-line therapy for advanced or metastatic BTC, focusing on progression-free survival and objective response rate.

What efficacy results were reported for the treatment regimen?

Among 30 enrolled patients, the objective response rate was 13.0%, with median PFS of 5.3 months and median overall survival of 11.7 months.

Did PD-L1 expression or tumor mutational burden (TMB) predict benefit?

No. Subgroup analyses showed no significant association between PD-L1 status or TMB level and improved PFS.

What safety outcomes were observed?

All patients experienced adverse events, with grade 3–4 events in 26.7% of patients. Common events included anemia (20.0%), leukocytopenia (13.3%), and nausea (6.6%), and no grade 5 AEs were observed.

Sep 30, 2026

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