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

Author

Listed:
  • Jingjing Li

    (Wenzhou Medical University
    Zhejiang Cancer Hospital
    Chinese Academy of Sciences)

  • Shurui Zhou

    (Zhejiang Cancer Hospital
    Chinese Academy of Sciences
    Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province)

  • 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
    Chinese Academy of Sciences
    Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province)

  • 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
    Zhejiang Cancer Hospital
    Chinese Academy of Sciences
    Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province)

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.

Suggested Citation

  • 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 &, 2025. "Sintilimab and anlotinib with gemcitabine plus cisplatin in advanced biliary tract cancer: SAGC a randomized phase 2 trial," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60119-3
    DOI: 10.1038/s41467-025-60119-3
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