Efficacy and safety of pembrolizumab, lenvatinib, and reduced-dose gemcitabine/oxaliplatin as initial treatment for advanced biliary tract cancer - a multicenter, single-arm, prospective, phase II study

Sep 23, 2026

Uploaded by Jacob

Biliary tract cancer is a aggressive malignancy with limited options and poor prognosis, while immune checkpoint inhibitor combinations can improve outcomes but raise concerns about toxicity. This phase II multicenter single-arm study assessed pembrolizumab plus lenvatinib combined with reduced-dose gemcitabine and oxaliplatin as first-line therapy. Sixty unresectable or metastatic patients received treatment for 6–8 cycles then maintenance. The primary endpoint was objective response rate, with progression-free and overall survival and safety. Results showed an ORR of 55.0% and 93.3% disease control, with manageable grade 1–2 events and no treatment-related deaths.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

What is already known on this topic

What this study adds

How this study might affect research, practice or policy

Introduction

Open access Original research Efficacy and safety of pembrolizumab, lenvatinib, and reduced-dose gemcitabine/oxaliplatin as initial treatment for advanced biliary tract cancer: a multicenter, single-arm, prospective, phase II study Mingjian Piao,1 Chengjie Li,1 Shuofeng Li ,1 Nan Zhang,1 Jiongyuan Li,1 Xu Luo,2 Rong Liu,3 Fei Wang,3 Xiangde Shi,4 Chao Liu,4 Guang Tan,2 Zhenyu Zhu,5 Xiaobo Yang,1 Haitao Zhao 1 To cite: Piao M, Li C, Li S, et al. Efficacy and safety of pembrolizumab, lenvatinib, and reduced-dose gemcitabine/ oxaliplatin as initial treatment for advanced biliary tract cancer: a multicenter, singlearm, prospective, phase II study. Journal for ImmunoTherapy of Cancer 2026;14:e014653 . doi:10.1136/jitc-2025-014653 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2025-014653](jitc-2025-014653)) . MP, CL, SL and NZ are joint first authors. Accepted 28 January 2026 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Dr Haitao Zhao; [zhaoht@pumch.cn](zhaoht@pumch.cn) Dr Zhenyu Zhu; [zhuzy302@163.com](zhuzy302@163.com) Dr Guang Tan; [tanguang009@sina.com](tanguang009@sina.com) Dr Xiaobo Yang; [yangxiaobo67@pumch.cn](yangxiaobo67@pumch.cn) ABSTRACT Background Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitors combined with chemotherapy have improved patient outcomes, their toxicity remains concerning. This phase II multicenter trial evaluated the efficacy and safety of pembrolizumab plus lenvatinib with a reduced-dose gemcitabine and oxaliplatin (GEMOX) regimen as a first-line therapy for advanced BTC. Methods 60 patients with unresectable or metastatic BTC were enrolled from five centers in China. Patients received pembrolizumab (200 mg, every 3 weeks), lenvatinib (8 or 12 mg daily), and modified GEMOX (gemcitabine 1000 mg/m² and oxaliplatin 85 mg/m² on day 1 of each 3-week cycle) for 6–8 cycles, followed by maintenance with pembrolizumab and lenvatinib. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results At a median follow-up of 16.0 months, the ORR (complete response 5 .0%, partial response (PR) 50.0%) and disease control rate were 55 .0% and 93 .3%, respectively. The median PFS and OS were 12.5 months (95% CI 7.93 to 16.3), and 19.5 months (95% CI 17.97 to not estimable), respectively. Elevated baseline CA19-9 (>37 U/mL) and carcinoembryonic antigen levels (>5 ng/ mL) were independently associated with poor OS and PFS, respectively. The regimen showed manageable toxicity, with 95% of patients experiencing treatment-emergent adverse events (AEs), mostly grades 1–2; grade 3–4 AEs occurred in 65% of patients, with no treatment-related deaths. Immune-related AEs occurred in 11.7% of the patients and were predominantly mild. Conclusions Pembrolizumab plus lenvatinib with reduced-dose GEMOX demonstrated promising efficacy and a favorable safety profile in advanced BTC, suggesting that chemotherapy de-escalation may optimize the efficacy–toxicity balance. Further randomized studies are warranted to confirm these findings and refine biomarkerbased treatment selections. WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Chemo-immunotherapy has become the standard first-line treatment for advanced biliary tract cancer, and early studies combining anti-PD-1 antibodies with anti-angiogenic agents such as lenvatinibhave shown encouraging activity in small cohorts. However, these regimens typically rely on full-dose cytotoxic chemotherapy, which leads to substantial toxicity and attrition in

FAQs

What treatment combination was evaluated for advanced biliary tract cancer in this phase II trial?

The study evaluated pembrolizumab plus lenvatinib together with a reduced-dose gemcitabine and oxaliplatin (GEMOX) regimen as initial first-line treatment.

What were the primary and key secondary endpoints?

The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

What efficacy and safety outcomes were reported at median follow-up of 16.0 months?

ORR was 55.0% with a disease control rate of 93.3%, and median PFS and OS were 12.5 and 19.5 months, respectively. Toxicity was manageable, with most adverse events being grades 1–2 and no treatment-related deaths.

Sep 23, 2026

Uploaded by Jacob