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Publications

Journal Article Clinical Trial, Phase II Randomized Controlled Trial Epublish

PubMed: 40593475 DOI: 10.1038/s41467-025-60119-3

Sintilimab and anlotinib with gemcitabine plus cisplatin in advanced biliary tract cancer: SAGC a randomized phase 2 trial.

Nat Commun 16(1):5559

Authors: Jingjing Li, Shurui Zhou, Xiaoqing Xu, Qinhong Zheng, Fabiao Zhang, Cong Luo, Da Li, Xing Sun, Zhe Han, Wei Wu, Junrong Yan, Yang Shao, Yuhua Zhang, Bingchen Wu, Qing Wei, Xinbao Wang, Yiwen Zhou, Weijing Sun, Qi Xu, Jieer Ying

Affiliations

  • Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China.
  • Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
  • Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.
  • Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, Zhejiang, PR China.
  • Department of Medical Oncology Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, PR China.
  • Department of Hepatic-Biliary-Pancreatic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, Zhejiang, PR China.
  • Department of Medical Oncology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University, School of Medicine, Hangzhou, Zhejiang, PR China.
  • Innovent Biologics, Inc. Suzhou, Jiangsu, China.
  • Radiology Department, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.
  • Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.
  • Geneseeq Research Institute, Nanjing Geneseeq Technology Inc. Nanjing, PR China.
  • Hepatobiliary and Pancreatic Surgery Department, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.
  • Department of Oncology, Hospital of Chinese Medicine of Changxing, Huzhou, PR China.
  • The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • Division of Medical Oncology, University of Kansas School of Medicine, Westwood, KS, USA.
  • Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China.
  • Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
  • Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.
  • Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, Zhejiang, PR China.

Abstract

Biliary tract cancer (BTC) has a poor prognosis with limited treatment options. This phase 2 trial randomized 80 patients with unresectable/metastatic BTC 1:1 to sintilimab, anlotinib, and gemcitabine/cisplatin (SAGC) or chemotherapy alone (GC). At 13.4-month median follow-up, SAGC significantly improved median progression-free survival (8.5 vs. 6.3 months; HR 0.48, 95% CI 0.22-0.64, p = 0.005) and objective response rate (51.4% vs. 29.4%), with higher grade 3/4 adverse events (75.0% vs. 43.6%). Post hoc analysis showed enhanced efficacy with anlotinib 8 mg versus 10 mg (ORR 54.5% vs. 38.8%). In AKT/YAP tumor models, low-dose anlotinib (3 mg/kg) combined with sintilimab improved vascular perfusion, T-cell cytotoxicity, and cytokine secretion compared to high-dose (6 mg/kg). These findings demonstrate improved efficacy and manageable toxicity with SAGC, particularly at the 8 mg anlotinib dose, suggesting low-dose regimens may optimize antitumor response while mitigating adverse effects. Trial registration number ClinicalTrials.gov Identifier: NCT04300959.

MeSH

Biliary Tract Neoplasms, Neoplasms, Biliary Tract