Anlotinib+Cadonilimab+PULSAR in Advanced Biliary Tract Cancer

Summary

This study aims to evaluate the safety and preliminary efficacy of anlotinib combined with cadonilimab and PULSAR in previously treated advanced unresectable or netastatic biliary tract cancer.

Timeline

Start

2026-06-03

Primary completion

2027-06-30

Completion

2028-06-30

Publications

• Background Moore C, Hsu CC, Chen WM, Chen BPC, Han C, Story M, Aguilera T, Pop LM, Hannan R, Fu YX, Saha D, Timmerman R. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Preclinical Models Enhances Single-Agent Immune Checkpoint Blockade. Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1306-1316. doi: 10.1016/j.ijrobp.2021.03.047. Epub 2021 Mar 29.
• Background Peng H, Moore C, Zhang Y, Saha D, Jiang S, Timmerman R. An AI-based approach for modeling the synergy between radiotherapy and immunotherapy. Sci Rep. 2024 Apr 8;14(1):8250. doi: 10.1038/s41598-024-58684-6.
• Background Rouf S, Moore C, Saha D, Nguyen D, Bleile M, Timmerman R, Peng H, Jiang S. PULSAR Effect: Revealing potential synergies in combined radiation therapy and immunotherapy via differential equations. J Theor Biol. 2025 Jan 7;596:111974. doi: 10.1016/j.jtbi.2024.111974. Epub 2024 Oct 22.
• Background Peng H, Moore C, Saha D, Jiang S, Timmerman R. Understanding the PULSAR effect in combined radiotherapy and immunotherapy using transformer-based attention mechanisms. Front Oncol. 2024 Dec 2;14:1497351. doi: 10.3389/fonc.2024.1497351. eCollection 2024.
• Background Chen B, Yao W, Li X, Lin G, Chu Q, Liu H, Du Y, Lin J, Duan H, Wang H, Xiao Z, Sun H, Liu L, Xu L, Xu Y, Xu F, Kong Y, Pu X, Li K, Wang Q, Li J, Li B, Xia Y, Wu L. A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer. Br J Cancer. 2024 Feb;130(3):450-456. doi: 10.1038/s41416-023-02519-0. Epub 2023 Dec 18.
• Background Li J, Zhou S, Xu X, Zheng Q, Zhang F, Luo C, Li D, Sun X, Han Z, Wu W, Yan J, Shao Y, Zhang Y, Wu B, Wei Q, Wang X, Zhou Y, Sun W, Xu Q, Ying J. Sintilimab and anlotinib with gemcitabine plus cisplatin in advanced biliary tract cancer: SAGC a randomized phase 2 trial. Nat Commun. 2025 Jul 1;16(1):5559. doi: 10.1038/s41467-025-60119-3.
• Background Liu L, Chen B, Tang M, Guo Y, Hou J, Zhou W, Zhu X. Combination of anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report. Anticancer Drugs. 2024 Sep 1;35(8):752-756. doi: 10.1097/CAD.0000000000001619. Epub 2024 May 10.
• Background Zhou M, Jin Y, Zhu S, Xu C, Li L, Liu B, Shen J. A phase II study to evaluate the safety and efficacy of anlotinib combined with toripalimab for advanced biliary tract cancer. Clin Transl Immunology. 2024 Jan 12;13(1):e1483. doi: 10.1002/cti2.1483. eCollection 2024.
• Background Zhou J, Sun Y, Zhang W, Yuan J, Peng Z, Wang W, Gong J, Yang L, Cao Y, Zhao H, Chen C, Wang W, Shen L, Zhou A. Phase Ib study of anlotinib combined with TQB2450 in pretreated advanced biliary tract cancer and biomarker analysis. Hepatology. 2023 Jan 1;77(1):65-76. doi: 10.1002/hep.32548. Epub 2022 Aug 18.
• Background Li D, Chi Y, Chen X, Ge M, Zhang Y, Guo Z, Wang J, Chen J, Zhang J, Cheng Y, Li Z, Liu H, Qin J, Zhu J, Cheng R, Xu Z, Zheng X, Tang P, Gao M. Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial. Clin Cancer Res. 2021 Jul 1;27(13):3567-3575. doi: 10.1158/1078-0432.CCR-20-2950. Epub 2021 Apr 8.
• Background Chi Y, Fang Z, Hong X, Yao Y, Sun P, Wang G, Du F, Sun Y, Wu Q, Qu G, Wang S, Song J, Yu J, Lu Y, Zhu X, Niu X, He Z, Wang J, Yu H, Cai J. Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma. Clin Cancer Res. 2018 Nov 1;24(21):5233-5238. doi: 10.1158/1078-0432.CCR-17-3766. Epub 2018 Jun 12.
• Background Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.
• Background Mie T, Sasaki T, Okamoto T, Furukawa T, Takeda T, Kasuga A, Ozaka M, Sasahira N. Current Status of Targeted Therapy for Biliary Tract Cancer in the Era of Precision Medicine. Cancers (Basel). 2024 Feb 22;16(5):879. doi: 10.3390/cancers16050879.
• Background Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. doi: 10.1016/S1470-2045(21)00027-9. Epub 2021 Mar 30.
• Background Zhang D, Dorman K, Westphalen CB, Haas M, Ormanns S, Neumann J, Seidensticker M, Ricke J, De Toni EN, Klauschen F, Algul H, Reislander T, Boeck S, Heinemann V. Unresectable biliary tract cancer: Current and future systemic therapy. Eur J Cancer. 2024 May;203:114046. doi: 10.1016/j.ejca.2024.114046. Epub 2024 Apr 12.
• Background Vogel A, Bridgewater J, Edeline J, Kelley RK, Klumpen HJ, Malka D, Primrose JN, Rimassa L, Stenzinger A, Valle JW, Ducreux M; ESMO Guidelines Committee. Electronic address: [email protected]. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Feb;34(2):127-140. doi: 10.1016/j.annonc.2022.10.506. Epub 2022 Nov 10. No abstract available.
• Background Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

Drugs

Indications