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Active, not recruitingNCT07635290Updated Jun 9, 2026

Anlotinib+Cadonilimab+PULSAR in Advanced Biliary Tract Cancer

A Phase 2 interventional study of Anlotinib + Cadonilimab and PULSAR in Previously Treated, Advanced and Biliary Tract Cancers, sponsored by West China Hospital. Active, not recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-06-09.

Sponsored by West China Hospital · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Previously Treated, Advanced
  • Biliary Tract Cancers

Keywords

  • immunotherapy
  • targeted therapy
  • radiotherapy
  • BTC
03

In context

Biliary Tract Neoplasms

484 studies on the registry are indexed under Biliary Tract Neoplasms; 187 are open to participants now.

This study's planned enrollment of 26 is below the median of 56 across 404 interventional studies indexed under Biliary Tract Neoplasms.

Browse Biliary Tract Neoplasms studies →

Lead sponsor

West China Hospital is the lead sponsor of 483 studies on the registry; 240 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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.
  • Occurrence of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to first dose.
  • Any clinically significant laboratory or physical abnormality that, in the investigator's opinion, may affect safety evaluation, such as: active infection requiring systemic treatment, uncontrolled diabetes, hypertension that cannot be controlled to within normal range (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg) after treatment with ≤ 2 antihypertensive drugs, myocardial infarction within the past 6 months, thyroid dysfunction ( > NCI CTCAE v5.0 Grade 1), etc.
  • Any other condition that the investigator considers inappropriate for enrollment.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
26 participants (estimated)

Study arms

  • Experimental
    Anlotinib + Cadonilimab + PULSAR

    Drug: Anlotinib + Cadonilimab · Radiation: PULSAR

Interventions

  • DrugAnlotinib + Cadonilimab

    Anlotinib Combined with Cadonilimab

  • RadiationPULSAR

    Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy

06

What researchers measure

Primary outcomes

  1. Objective response rate (RECIST v1.1)

    Time frame: From the first patient enrollment until 6 months after the last patient enrollment

Secondary outcomes

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

    the incidence of adverse events (AE) or severe adverse events (SAE) assessed by CTCAE v5.0

    Time frame: From the first patient enrollment until 6 months after the last patient enrollment

  2. Progression free survival

    Time frame: From the first patient enrollment until 6 months after the last patient enrollment

  3. Overall survival

    Time frame: From the first patient enrollment until 6 months after the last patient enrollment

07

Study locations

1 site
  • West China Hospital, Sichuan University
    Chengdu, Sichuan 610041, China
08

References and documents

Publications

  • 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. PubMed 33794306 ↗
  • 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. PubMed 38589494 ↗
  • 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. PubMed 39448025 ↗
  • 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. PubMed 39687891 ↗
  • 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. PubMed 38110665 ↗
  • 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. PubMed 40593475 ↗
  • 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. PubMed 38728054 ↗
  • 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. PubMed 38223257 ↗
  • 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. PubMed 35491432 ↗
  • 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. PubMed 33832949 ↗
  • 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. PubMed 29895706 ↗
  • 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. PubMed 29438373 ↗
  • 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. PubMed 38473240 ↗
  • 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. PubMed 33798493 ↗
  • 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. PubMed 38626513 ↗
  • 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. PubMed 36372281 ↗
  • 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. PubMed 38572751 ↗

Individual participant data

Plan to share: Undecided — IPD will not be shared in order to protect participant confidentiality, in compliance with local data protection regulations and ethical committee requirements. Additionally, IPD sharing is restricted under contractual agreements with study sponsors/partners, who retain data ownership for independent analyses. Given the complexity and size of the dataset (e.g., genomic/imaging data), anonymized IPD sharing is technically unfeasible without risking data integrity. Furthermore, to safeguard intellectual property rights and permit ongoing secondary analyses by the research team, IPD will be retained internally.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 9, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT07635290
Lead sponsor
West China Hospital
Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Akeso
Responsible party
Wang Xin (Professor, West China Hospital) — Principal investigator
First posted
Jun 9, 2026
Start date
Jun 3, 2026
Primary completion
Jun 30, 2027 (estimated)
Completion
Jun 30, 2028 (estimated)
Last update
Jun 9, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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