Cryoablation Combined With QL1706 (Iparomlimab/Tuvonralimab) Plus Lenvatinib in Patients With Advanced Biliary Tract Cancer.

NCT07829874 | Not Yet Recruiting Phase 2

• 1 other identifier: CASTLE-ZS-04
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of cryoablation combined with QL1706 (iparomlimab/tuvonralimab) plus lenvatinib in patients with advanced biliary tract cancer (BTC) who have progressed after first-line treatment.

Conditions

Biliary Tract Cancer (BTC)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.

  24 months

Secondary Outcomes (7)

• Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1

  24 months

• Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1

  24 months

• Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1

  24 months

• Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1

  24 months

• Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1

  42 months

Study Arms (6)

ICC-01

EXPERIMENTAL

Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib

ICC-02

EXPERIMENTAL

Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib+cryoablation

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib; Procedure: Cryoablation

ECC-01

EXPERIMENTAL

Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib

ECC-02

EXPERIMENTAL

Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib +cryoablation

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib; Procedure: Cryoablation

GBC-01

EXPERIMENTAL

Gallbladder cancer (GBC) received QL1706 + lenvatinib

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib

GBC-02

EXPERIMENTAL

Gallbladder cancer (GBC) received QL1706 + lenvatinib+cryoablation

Drug: QL1706 (Iparomlimab/Tuvonralimab); Drug: Lenvatinib; Procedure: Cryoablation

Interventions

QL1706 (Iparomlimab/Tuvonralimab) DRUG

A bifunctional PD1/CTLA4 dual blocker

ECC-01; ECC-02; GBC-01; GBC-02; ICC-01; ICC-02

Lenvatinib DRUG

An TKI.

ECC-01; ECC-02; GBC-01; GBC-02; ICC-01; ICC-02

Cryoablation PROCEDURE

Cryoablation will be performed with a two-cycle freeze-thaw phase protocol; US or non-contrast CT images will be obtained to visualize the evolving ablation zone

ECC-02; GBC-02; ICC-02

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained.
• Age ≥ 18 years at time of study entry.
• Participants must have unresectable or metastatic histologically confirmed biliary tract cancer.
• Participants must have failed 1 line of GemCis plus PD1/PD-L1 inhibitor for advanced cholangiocarcinoma due to disease progression or toxicity.
• At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
• Performance status (PS) ≤ 2 (ECOG scale).
• Life expectancy of at least 12 weeks.
• Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

You may not qualify if:

• History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
• Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
• Prior treatment with cryoablation.
• RFA and resection administered less than 4 weeks prior to study treatment start.
• Radiotherapy administered less than 4 weeks prior to study treatment start.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
• Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
• Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to: a) history of interstitial lung disease b) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) c) known acute or chronic pancreatitis d) active tuberculosis e) any other active infection (viral, fungal or bacterial) requiring systemic therapy f) history of allogeneic tissue/solid organ transplant g) diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. i) Live vaccine within 30 days prior to the first dose of treatment or during study treatment. j) History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
• Medication that is known to interfere with any of the agents applied in the trial.
• Any other efficacious cancer treatment except protocol specified treatment at study start.
• Patient has received any other investigational product within 28 days of study entry.
• Prior therapy with an anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). \[Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner\]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

lenvatinib; Cryosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Peng Wang

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Wang

CONTACT

86-21-64041990; peng_wang@fudan.edu.cn

Study Design

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

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 21, 2026
• Study Start: September 20, 2026
• Primary Completion (Estimated): September 20, 2028
• Study Completion (Estimated): September 20, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)