Phase II Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Albumin-Bound Paclitaxel and Lenvatinib as Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer

Recruiting now · Phase 2

Conditions studied: Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer

In brief

Biliary tract carcinoma (BTC) is a highly aggressive malignancy with rising incidence worldwide. Most patients present at an advanced stage and have a dismal prognosis. First-line gemcitabine-platinum plus PD-1/PD-L1 blockade has become the new standard, yet no established second-line therapy exists after progression on this regimen. Combining dual checkpoint inhibition (PD-1/CTLA-4) with anti-angiogenic therapy and chemotherapy may overcome primary resistance.Although several studies have evaluated immune-checkpoint inhibitors (ICIs) alone or combined with anti-angiogenic agents in advanced BTC, overall survival improvements remain modest, and enrolled patients have typically progressed after chemotherapy only. Thus, the optimal second-line regimen in the immunotherapy era-especially the efficacy and safety of combining ICIs with chemotherapy-warrants further investigation.Dual PD-1/PD-L1 plus CTLA-4 blockade can comprehensively reactivate anti-tumor immunity by relieving T-cell suppression and enhancing cytotoxic function. QL1706, developed by Qilu Pharmaceutical using the proprietary MabPair™ platform, is the first bispecific antibody simultaneously targeting PD-1 and CTLA-4, showing synergistic anti-tumor activity and favorable tolerability. Lenvatinib is a multi-target tyrosine-kinase inhibitor with anti-angiogenic and immunomodulatory properties.For patients progressing after first-line therapy, preliminary data indicate that combining ICIs with anti-angiogenic agents (VEGFR2 antibodies or TKIs) yields modest efficacy; however, prospective evidence-especially for those refractory to chemotherapy plus PD-1/PD-L1 inhibitors-is lacking. Therefore, we designed an exploratory clinical trial evaluating QL1706 combined with albumin-bound paclitaxel and lenvatinib as second-line treatment for unresectable or metastatic BTC, aiming to provide a safe and effective option, particularly for patients previously exposed to PD-1/PD-L1 inhibitors, to prolong survival and improve quality of life.

Key facts

Study ID

NCT07530445

Run by

Sun Yat-sen University

People needed

40

Starts

2026-03-23

Expected to finish

2027-12-30

Last updated by the study team

2026-04-15

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects voluntarily agree to participate in the study, sign the informed-consent form, demonstrate good compliance, and are willing to attend follow-up visits.
• Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary-tract cancer (gallbladder carcinoma, cholangiocarcinoma, or ampullary carcinoma of pancreaticobiliary type).
• Age 18-70 years (inclusive) at the time of informed consent, either male or female.
• ECOG performance status 0-1 and life expectancy ≥ 12 weeks.
• Received one prior line of systemic therapy containing a platinum agent, gemcitabine, or fluoropyrimidine (non-taxane), with or without PD-1/PD-L1 antibody.
• Patients who develop distant metastasis after curative-intent surgery are eligible if they received adjuvant chemotherapy without a taxane and relapse < 6 months after completion of adjuvant therapy.
• At least one measurable lesion according to RECIST v1.1:
• <!-- -->
• .Lesion diameter ≥ 10 mm on contrast-enhanced MRI or CT.
• .Lesions treated with prior local therapy may be considered measurable if they have progressed and meet RECIST v1.1 criteria.
• .Lesions previously treated with radioactive seed implantation cannot be used as target lesions.
• No clinically significant cardiovascular, pulmonary, cerebral, or other major organ dysfunction.
• Adequate Major Organ and Bone-Marrow Function Criteria
• Hematology • White blood cell (WBC) count ≥ 4.0 × 10⁹/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count ≥ 75 × 10⁹/L
• Hemoglobin ≥ 80 g/L
• Coagulation
• International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN)
• Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN
• Liver Function
• Total serum bilirubin ≤ 1.5 × ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN - Patients with concurrent liver metastases may be enrolled if ALT/AST ≤ 5 × ULN
• For obstructive jaundice: serum total bilirubin must be ≤ 1.5 × ULN after adequate internal or external biliary drainage
• Serum albumin ≥ 30 g/L

You may not qualify if…

• Known hypersensitivity to any component of the study drugs (QL1706, albumin-bound paclitaxel, or lenvatinib).
• Prior anti-cancer therapy within specified wash-out periods before the first dose of study treatment:
• Fluoropyrimidines (e.g., S-1, capecitabine): ≤ 2 weeks
• Other cytotoxic chemotherapy: ≤ 3 weeks
• Small-molecule targeted therapy: ≤ 2 weeks
• Biologic therapy, large-molecule targeted therapy, or immunotherapy: ≤ 4 weeks
• Histologic diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or undifferentiated carcinoma of the biliary tract.
• Obstructive jaundice that has not been adequately relieved (bilirubin not reduced to protocol-specified limits).
• Other malignancies within the past 5 years, except adequately treated basal-cell or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix.
• Any history or current evidence of brain metastases.
• Hepatic tumor burden ≥ 70 % of total liver volume, as determined by the investigator.
• Major surgery or invasive procedure within 4 weeks prior to enrollment, unless wound healing is complete (exceptions: venous catheterization, percutaneous drainage, or biliary drainage for obstructive jaundice).
• Loco-regional anti-tumor therapy within 4 weeks, including trans-arterial chemoembolization (TACE), cryoablation, or radiofrequency ablation of liver metastases.
• Clinically significant electrolyte disturbances, as judged by the investigator.
• Uncontrolled hypertension (systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg) despite optimal medical management.
• High risk of fatal vascular invasion/bleeding in the opinion of the investigator (e.g., tumor likely to erode a major vessel during the study).
• Bleeding diathesis or significant bleeding history within 3 months, including:
• > 30 mL bleeding, hematemesis, melena, or hematochezia
• Hemoptysis (> 5 mL fresh blood within 4 weeks)
• Congenital or acquired coagulopathy
• Clinically relevant hemorrhagic events (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer).
• Clinically significant cardiovascular disease, including:
• Acute myocardial infarction, severe/unstable angina, or coronary artery bypass graft surgery within 6 months
• New York Heart Association (NYHA) class > II congestive heart failure
• Symptomatic ventricular arrhythmias requiring medication

Where it is running

• Zhiqiang Wang, guangzhou, Other (Non U.S.) 510000 Recruiting — Guangzhou, China (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.