Disitamab vedotin in combination with lenvatinib for patients with HER2-positive unresectable locally advanced or metastatic biliary tract cancer - study protocol of a phase II clinical trial

Sep 23, 2026

Introduction: Chemotherapy remains a standard second-line option for advanced biliary tract cancer (BTC) but offers suboptimal efficacy. Disitamab vedotin (RC48) and lenvatinib have shown promising activity in HER2-positive BTC and other malignancies. This phase II exploratory trial evaluates the efficacy and safety of RC48 plus lenvatinib in HER2-positive advanced BTC from second-line or beyond after prior treatment failure. Methods and analysis: A single-centre, single-arm, open-label study enrolls 31 patients; primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, progression-free survival, and overall survival.

LanguageEnglish

CategoryHealthcare

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Pages8

Reading Time20 min

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ABSTRACT

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

INTRODUCTION

Background on BTC and current therapies

STRENGTHS AND LIMITATIONS OF THIS STUDY

Open access Protocol To cite: Yang Y, Zhang J, Wu Z, et al. Disitamab vedotin in combination with lenvatinib for patients with HER2-positive unresectable locally advanced or metastatic biliary tract cancer: study protocol of a phase II clinical trial. BMJ Open 2026;16:e097647 . doi:10 . 1136/ bmjopen-2024-097647 ► Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[bmjopen-2024-097647](bmjopen-2024-097647)) . YY, JZ and ZW contributed equally. Received 06 December 2024 Accepted 13 November 2025 © 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 Gang Wu; [xhzlwg@163.com](xhzlwg@163.com) Disitamab vedotin in combination with lenvatinib for patients with HER2-positive unresectable locally advanced or metastatic biliary tract cancer: study protocol of a phase II clinical trial Yongqiang Yang ,1,2,3 Jinfeng Zhang ,1,2,3 Zilong Wu ,1,2,3 Dongen Liu ,1,2,3 Jing Tang ,1,2,3 Jun Xue ,1,2,3 Gang Wu 1,2,3 ABSTRACT Introduction Chemotherapy is the standard second-line treatment option for advanced biliary tract cancer (BTC), but its therapeutic efficacy is suboptimal. Disitamab vedotin (RC48) and lenvatinib have demonstrated promising efficacy in human epidermal growth factor receptor 2 (HER2)-positive BTC and other malignancies. In this study, we aim to evaluate the efficacy and safety of RC48 in combination with lenvatinib in second-line or above treatment for HER2-positive advanced BTC. Methods and analysis This is a single-centre, singlearm, open-label, exploratory phase II clinical study inpatients with HER2-positive unresectable locally advanced or metastatic BTC who have failed prior therapy. 31 patients will be enrolled in this study to receive the combination of RC48 and lenvatinib. The primary study endpoint is objective response rate, and the secondary study endpoints are disease control rate, duration of response, progression-free survival and overall survival. Ethics and dissemination The study has received approval from the Medical Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval No. (2023)0367-01) . Results will be disseminated through publication in peerreviewed journals and through other appropriate media channels. Trial registration number ChiCTR2300076406 . INTRODUCTION Biliary tract cancer (BTC), including intrahepatic and extrahepatic BTC and gallbladder cancer, accounts for 4% of malignant tumours in the digestive system and is oneof the most common causes of cancerrelated deaths, with its incidence gradually increasing worldwide.1–3 BTC lacks specific symptoms, making it difficult to detect in the early stage, and the majority of patients are already in the advanced stage at the time of diagnosis.4 5 Even after surgical resection, BTC exhibits high rates of both distant and locoregional recurrence, with approximately STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ This study evaluates the efficacy and safety of combining antibody-drug conjugates with tyrosine kinase inhibitors in advanced biliary tract cancer. ⇒ Both disitamab vedotin and lenvatinib have shown promising efficacy in previous clinical trials, with potential for synergistic effects in combination. ⇒ The study employs a pragmatic clinical trial design, with real-world clinical alignment in background, inclusion criteria, interventions and outcomes. ⇒ A single-arm design and small sample size may introduce selection bias and confounding factors, impacting the accuracy of efficacy assessment. ⇒ Missing data and intercurrent events will be handled with multiple imputation and intention-to-treat analysis. 60

FAQs

What treatment does the phase II study evaluate for HER2-positive advanced biliary tract cancer?

The study evaluates disitamab vedotin (RC48) in combination with lenvatinib for patients with HER2-positive unresectable locally advanced or metastatic BTC who have failed prior therapy.

How many participants will be enrolled, and what is the study design?

A single-centre, single-arm, open-label exploratory phase II clinical study will enroll 31 patients.

What is the primary endpoint and which secondary outcomes will be measured?

The primary endpoint is objective response rate. Secondary endpoints include disease control rate, duration of response, progression-free survival, and overall survival.

Sep 23, 2026

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