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

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 () and Jieer Ying ()
Additional contact information
Jingjing Li: Zhejiang Cancer Hospital
Shurui Zhou: Zhejiang Cancer Hospital
Xiaoqing Xu: Zhejiang Cancer Hospital
Qinhong Zheng: Quzhou People’s Hospital
Fabiao Zhang: Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province
Cong Luo: Zhejiang Cancer Hospital
Da Li: School of Medicine
Xing Sun: Innovent Biologics, Inc.
Zhe Han: Chinese Academy of Sciences
Wei Wu: Chinese Academy of Sciences
Junrong Yan: Nanjing Geneseeq Technology Inc.
Yang Shao: Nanjing Geneseeq Technology Inc.
Yuhua Zhang: Chinese Academy of Sciences
Bingchen Wu: Hospital of Chinese Medicine of Changxing
Qing Wei: Zhejiang Cancer Hospital
Xinbao Wang: Chinese Academy of Sciences
Yiwen Zhou: Zhejiang Chinese Medical University
Weijing Sun: University of Kansas School of Medicine
Qi Xu: Zhejiang Cancer Hospital
Jieer Ying: Wenzhou Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60119-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60119-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60119-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().