Anlotinib+Cadonilimab+PULSAR in Advanced Biliary Tract Cancer

NCT07635290 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: PRIM-C2
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Previously Treated, Advanced; Biliary Tract Cancers

Keywords

immunotherapy; targeted therapy; radiotherapy; BTC

Outcome Measures

Primary Outcomes (1)

• Objective response rate (RECIST v1.1)

  From the first patient enrollment until 6 months after the last patient enrollment

Secondary Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  From the first patient enrollment until 6 months after the last patient enrollment

• Progression free survival

  From the first patient enrollment until 6 months after the last patient enrollment

• Overall survival

  From the first patient enrollment until 6 months after the last patient enrollment

Study Arms (1)

Anlotinib + Cadonilimab + PULSAR

EXPERIMENTAL

Drug: Anlotinib + Cadonilimab; Radiation: PULSAR

Interventions

PULSAR RADIATION

Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy

Anlotinib + Cadonilimab + PULSAR

Anlotinib + Cadonilimab DRUG

Anlotinib Combined with Cadonilimab

Anlotinib + Cadonilimab + PULSAR

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-75 years, regardless of gender.
• Histopathologically confirmed diagnosis of biliary tract cancer (BTC).
• Patients with unresectable or metastatic BTC who have progressed after at least one line of standard systemic therapy
• At least one measurable lesion (RECIST v1.1) not previously irradiated.
• ECOG Performance Status (PS): 0-1.
• Expected survival ≥ 3 months.
• Willing and able to comply with study procedures, treatment, and follow-up.
• No contraindications to radiotherapy.
• Adequate organ function: WBC ≥ 2.5×10⁹/L, ANC ≥ 1.5×10⁹/L; PLT ≥ 75×10⁹/L; Hemoglobin (HGB) ≥ 90 g/L (no transfusion or EPO dependence within 7 days); Total bilirubin (Tbil) ≤ 1.5×ULN; ALT/AST ≤ 5×ULN;Albumin ≥ 30 g/L; INR ≤ 1.5×ULN; Serum creatinine (Cr) ≤ 1.5×ULN;Urine protein ≤ 1+
• Prior immunotherapy must have been discontinued for at least 4 weeks (to avoid cross-reactivity).
• Voluntary participation with signed informed consent form.

You may not qualify if:

• History of severe allergic reactions to chimeric, human, or humanized antibodies, or fusion proteins.
• Pregnant or lactating women; men or women of childbearing potential who are unwilling or unable to use effective contraception.
• History of other malignancies within the past 5 years, except for: malignancies treated with curative intent with no known active disease for ≥ 5 years prior to first dose and with low potential risk of recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease.
• Clinically symptomatic moderate to large volume pleural or peritoneal effusion.
• Active bleeding or coagulopathy (PT \> 16 s, APTT \> 43 s, INR \> 1.5 × ULN), bleeding tendency, or ongoing thrombolytic, anticoagulant, or antiplatelet therapy.
• History of gastrointestinal bleeding within the past 6 months, or clear evidence of gastrointestinal bleeding tendency, such as: known active localized ulcerative lesions, fecal occult blood ≥ 2+ (patients with persistent fecal occult blood 1+ should undergo gastroscopy).
• Severe gastric or esophageal varices requiring interventional treatment.
• Untreated active hepatitis B. (Note: Subjects with hepatitis B who are receiving antiviral therapy and have HBV viral load \< 2000 IU/mL may be permitted to participate in the study.)
• Active hepatitis C, defined as positive anti-HCV antibody or positive HCV-RNA with abnormal liver function.
• History of psychoactive substance abuse that cannot be discontinued, or history of psychiatric disorders.
• History of solid organ or bone marrow transplantation, or active autoimmune disease requiring systemic treatment within 2 years prior to first dose.
• Known immunodeficiency disease or HIV infection.
• Objective evidence of past or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired lung function.
• Major surgery (e.g., hepatic or other site) within 4 weeks prior to first dose, or minor surgery (e.g., simple excision, tooth extraction) within 1 week prior to first dose.
• Receipt of vaccination within 30 days prior to first dose.

Sponsors & Collaborators

• West China Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator
• Akeso: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (17)

• 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.

  PMID: 33794306 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.

  PMID: 38589494 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.

  PMID: 39448025 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.

  PMID: 39687891 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.

  PMID: 38110665 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.

  PMID: 40593475 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.

  PMID: 38728054 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.

  PMID: 38223257 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.

  PMID: 35491432 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.

  PMID: 33832949 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.

  PMID: 29895706 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.

  PMID: 29438373 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.

  PMID: 38473240 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.

  PMID: 33798493 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.

  PMID: 38626513 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: clinicalguidelines@esmo.org. 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.

  PMID: 36372281 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.

  PMID: 38572751 BACKGROUND

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

anlotinib; DEAE-Dextran

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dextrans; Glucans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 9, 2026
• Study Start: June 3, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 9, 2026

Record last verified: 2026-06

Locations

CN (1)