Tuvonralimab and Iparomlimab Based Regimens for the Neoadjuvant Treatment of Biliary Tract Cancer

NCT07267078 | Recruiting Phase 2 DMC

• 1 other identifier: QLIT-BTC
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Tuvonralimab/Iparomlimab-based neoadjuvant regimens can improve surgical and pathological outcomes in adults (≥18 years) with resectable or borderline-resectable biliary tract cancer (intrahepatic/extrahepatic cholangiocarcinoma or gallbladder cancer), ECOG 0-1, and no prior neoadjuvant therapy. The main questions it aims to answer are:

1. 1.Does the regimen increase the R0 resection rate (negative margins)?
2. 2.Does it raise major or pathologic complete response rates (MPR/pCR) and improve event-free survival (EFS) without increasing perioperative complications?

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• R0 Resection Rate

  Baseline (≤28 days before first dose); Neoadjuvant completion.

Study Arms (1)

Tuvonralimab/Iparomlimab combination

EXPERIMENTAL

Drug: Tuvonralimab/Iparomlimab combination with GEMOX chemotherapy

Interventions

Tuvonralimab/Iparomlimab combination with GEMOX chemotherapy DRUG

Tuvonralimab/Iparomlimab combination with GEMOX chemotherapy

Tuvonralimab/Iparomlimab combination

Eligibility Criteria

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

You may qualify if:

• The subjects voluntarily participated in the study and agreed to sign the written informed consent. They had good compliance and cooperated well with the follow-up.
• At the time of signing the informed consent form, the applicant was over 18 years old and could be of any gender.
• Patients with bile duct cancer diagnosed by histological or imaging methods, and whose imaging assessment or clinical assessment indicates borderline resectability
• There is at least one measurable lesion (as per the RECIST 1.1 criteria, this measurable lesion must have a spiral CT scan diameter of ≥ 10mm or the short diameter of a swollen lymph node of ≥ 15mm)
• Patient has not received any systematic treatment in the past
• The patient has locally advanced disease but no distant metastasis. Theoretically, a R0 resection can be achieved through complex resection combined with vascular reconstruction, but the risk is high.
• One of the following situations exists: 1. The main portal vein or a long segment of the hepatic artery on one side is affected, while the other side is still capable of supplying blood or draining. Vascular angioplasty or reconstruction can be performed. 2. The tumor involves the bile duct area beyond one secondary branch, but does not affect the primary branch on the opposite side. It is expected that the available residual liver and bile duct drainage can still be retained. 3. There is suspected regional lymph node metastasis (at the hepatic hilum, abdominal cavity), but there is no distant lymph node or peritoneal implantation.
• The ECOG score was 0-1 within one week before enrollment.
• The hematology and organ functions are adequate. Based on the laboratory test results obtained within 14 days prior to the start of the treatment (unless otherwise specified): Blood routine examination: (No blood transfusion, no use of G-CSF, no use of drugs for correction within 14 days before screening): Hb ≥ 90 g/L; Neutrophils ≥ 1.5 × 109/L; PLT ≥ 100 × 109/L. Biochemical examination: (No albumin transfusion within 14 days): Appropriate liver function: ALT and AST ≤ 2.5 × ULN; Bilirubin ≤ 2.0 × upper limit of normal; Appropriate renal function: Creatinine ≤ 1.5 × ULN, or creatinine clearance rate (CCr) \> 50 mL/min (using the standard Cockcroft-Gault formula)
• Fertile women: Agree to abstain from sexual intercourse (avoiding heterosexual intercourse) during the treatment period and for at least 6 months after the last administration (or use a contraceptive method with a failure rate of less than 1% for contraception)
• Men agree to abstain from sexual intercourse (not having sex with the opposite sex) or to use contraceptive measures, and agree not to donate sperm.

You may not qualify if:

• Has previously received any systemic treatment
• ECOG score \> 1 point
• It is confirmed that there is liver metastasis outside the liver.
• Pregnant women (with a positive pregnancy test before taking the medicine) or lactating women
• Those who are known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs, CTLA-4 monoclonal antibody drugs, or their components (or any excipients) are not eligible.
• Having undergone major surgical procedures (except for biopsy) within 4 weeks prior to the first drug treatment, or having an incomplete healing of the surgical incision
• Significant clinical cardiovascular and cerebrovascular diseases, including but not limited to acute myocardial infarction occurring within 6 months prior to enrollment, severe/unstable angina pectoris, cerebrovascular accident or transient cerebral ischemic attack, congestive heart failure (NYHA classification ≥ 2 grade); arrhythmias requiring anti-arrhythmic drug treatment (except for beta-blockers or digoxin); repeated electrocardiogram QTc interval \> 480 milliseconds (ms)
• Impaired liver and kidney functions, including conditions such as jaundice, ascites, and/or bilirubin levels \> 3×ULN, creatinine ratio \> 3.5g/24 hours, or renal failure requiring blood or peritoneal dialysis. And/or urine routine shows urine protein ≥ ++ or confirmed 24-hour urine protein quantification \> 1.0g
• There is a persistent infection of grade 2 or above (according to CTCAE version 5.0)
• Having a history of thromboembolic events within the past 6 months (including stroke and/or transient ischemic attack)
• Hypertension that has not been well controlled by antihypertensive drugs (systolic blood pressure \> 160 mmHg, diastolic blood pressure \> 100 mmHg)
• Participants who have had active autoimmune diseases or autoimmune disease history in the past two years; those who have active, known, or suspected autoimmune diseases that may affect important organ functions or who already/possibly require systemic immunosuppressive therapy.
• Known active central nervous system (CNS) metastasis and/or cancerous meningitis
• Be prepared or have previously undergone organ or allogeneic bone marrow transplantation
• A known history of active tuberculosis (with the tuberculosis bacteria)

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (2)

• Feng Bi et al. First-line iparomlimab and tuvonralimab (QL1706) or iparomlimab (QL1604) + bevacizumab (BEV) for unresectable hepatocellular carcinoma (HCC): Updated results from the phase Ib/II DUBHE-H-106 study.. JCO 43, 579-579(2025).

  RESULT

• Zhang Y, Huang Y, Yang Y, Zhao Y, Zhao H, Zhou N, Chen L, Zhou T, Chen G, Zhao S, Zhou H, Li H, Kang X, Zhang L, Fang W. Iparomlimab and tuvonralimab (QL1706) plus chemotherapy and bevacizumab for EGFR-mutant patients with advanced non-small cell lung cancer after failure of EGFR-tyrosine kinase inhibitors: updated results from cohort 5 in the DUBHE-L-201 study. J Hematol Oncol. 2025 Jul 26;18(1):75. doi: 10.1186/s13045-025-01728-9.

  PMID: 40713827 RESULT

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 5, 2025
• Study Start: May 25, 2025
• Primary Completion (Estimated): January 25, 2028
• Study Completion (Estimated): May 25, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)