Iparomlimab and Tuvonralimab with albumin‑bound paclitaxel and lenvatinib for second‑line advanced biliary tract cancer

A Single-Center, Single-Arm, Open-Label 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

This trial tests whether adding two immune antibodies (Iparomlimab and Tuvonralimab) to paclitaxel and lenvatinib can help people with unresectable or metastatic biliary tract cancer whose disease progressed after one prior platinum‑based or gemcitabine-containing regimen.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: lenvatinib, chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou)
• Trial ID: NCT07530445 on ClinicalTrials.gov

What this trial studies

This Phase II, single‑site interventional study combines a dual PD‑1/CTLA‑4 antibody regimen (QL1706: Iparomlimab and Tuvonralimab) with albumin‑bound paclitaxel and oral lenvatinib as second‑line therapy for unresectable or metastatic biliary tract cancer. QL1706 is given IV every three weeks at 5 mg/kg, albumin‑bound paclitaxel is given IV on days 1 and 8 of each 21‑day cycle at 125 mg/m2, and lenvatinib is taken daily at 8 mg orally. Eligible participants are 18–70 years old with ECOG 0–1, measurable disease by RECIST v1.1, and one prior systemic line that included platinum, gemcitabine, or a fluoropyrimidine. The goal is to determine safety and preliminary anti‑tumor activity in the post‑first‑line immunotherapy/chemotherapy era.

Who should consider this trial

Good fit: Ideal candidates are adults (18–70) with unresectable or metastatic biliary tract cancer, ECOG 0–1, at least one measurable lesion, and who received exactly one prior systemic chemotherapy line containing platinum, gemcitabine, or a fluoropyrimidine.

Not a fit: Patients with poor performance status (ECOG ≥2), inadequate organ function, more than one prior systemic line, prior taxane exposure as the only recent therapy, or without measurable disease are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could offer a new second‑line option that improves disease control and survival for patients who progressed after first‑line platinum/gemcitabine therapy.

How similar studies have performed: Previous studies combining immune checkpoint inhibitors with anti‑angiogenic agents in biliary tract cancer have shown only modest survival gains, and dual PD‑1/CTLA‑4 plus chemotherapy in the second‑line setting remains relatively novel and unproven.

Eligibility criteria

Inclusion Criteria:

1. Subjects voluntarily agree to participate in the study, sign the informed-consent form, demonstrate good compliance, and are willing to attend follow-up visits.
2. Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary-tract cancer (gallbladder carcinoma, cholangiocarcinoma, or ampullary carcinoma of pancreaticobiliary type).
3. Age 18-70 years (inclusive) at the time of informed consent, either male or female.
4. ECOG performance status 0-1 and life expectancy ≥ 12 weeks.
5. Received one prior line of systemic therapy containing a platinum agent, gemcitabine, or fluoropyrimidine (non-taxane), with or without PD-1/PD-L1 antibody.
6. 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.
7. At least one measurable lesion according to RECIST v1.1:

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1. .Lesion diameter ≥ 10 mm on contrast-enhanced MRI or CT.
2. .Lesions treated with prior local therapy may be considered measurable if they have progressed and meet RECIST v1.1 criteria.
3. .Lesions previously treated with radioactive seed implantation cannot be used as target lesions.

8.No clinically significant cardiovascular, pulmonary, cerebral, or other major organ dysfunction.

9.Adequate Major Organ and Bone-Marrow Function Criteria

1. 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
2. Coagulation

   * International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN)
   * Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN
3. 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
4. Renal Function

   * Serum creatinine ≤ 2 × ULN
   * Calculated creatinine clearance (CCr) ≥ 40 mL/min (Cockcroft-Gault or equivalent)
5. Urinalysis

   • Urine protein \< 2+ on dipstick

   \- If urine protein ≥ 2+, a 24-hour urine collection is required and must show total protein \< 1.0 g to permit enrollment
6. Thyroid Function

   • Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) all within ±10 % of the institutional normal range
   * Patients with non-autoimmune hypothyroidism whose FT3/FT4 levels are maintained within the normal range on stable replacement therapy are eligible
   * If TSH falls outside the above range, FT3, FT4, and clinical status must be assessed; subjects may be enrolled if findings indicate a non-acute, stable condition
7. Cardiac Function

   * Left ventricular ejection fraction (LVEF) ≥ 60 % as determined by two-dimensional echocardiography.

     10.Contraception requirements
   * Women of child-bearing potential must use a medically acceptable contraceptive method (e.g., IUD, oral contraceptive, condom) from screening through 6 months after the last dose of study drug; must have a negative serum or urine β-hCG test within 7 days before enrollment and must not be breastfeeding.
   * Men with partners of child-bearing potential must use effective contraception during the study and for 6 months after the last dose.

   Exclusion Criteria:
   1. Known hypersensitivity to any component of the study drugs (QL1706, albumin-bound paclitaxel, or lenvatinib).
   2. 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
   3. Histologic diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or undifferentiated carcinoma of the biliary tract.
   4. Obstructive jaundice that has not been adequately relieved (bilirubin not reduced to protocol-specified limits).
   5. 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.
   6. Any history or current evidence of brain metastases.
   7. Hepatic tumor burden ≥ 70 % of total liver volume, as determined by the investigator.
   8. 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).
   9. Loco-regional anti-tumor therapy within 4 weeks, including trans-arterial chemoembolization (TACE), cryoablation, or radiofrequency ablation of liver metastases.
   10. Clinically significant electrolyte disturbances, as judged by the investigator.
   11. Uncontrolled hypertension (systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg) despite optimal medical management.
   12. 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).
   13. 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).
   14. 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

       • QTc interval ≥ 480 ms on ECG.
   15. Active or uncontrolled severe infection ≥ CTCAE grade 2.
   16. Persistent toxicity \> CTCAE grade 2 from prior anti-cancer therapy (except alopecia, lymphopenia, or ≤ grade 2 oxaliplatin-related neuropathy). Patients with prior immune-related adverse events that have resolved to baseline or are stable on replacement therapy may be enrolled after specialist consultation.
   17. Pregnancy (positive pregnancy test) or lactation.
   18. Any condition that, in the investigator's opinion, would compromise patient safety or data integrity, including:

       • Seizure disorder requiring treatment

       • Clinically significant metabolic, physical, or laboratory abnormalities

       • Any disease state that could interfere with study participation or result in undue risk.
   19. Known HIV infection or clinically significant chronic liver disease, including:

       * Active hepatitis B virus (HBV) infection (HBV DNA \> 1 × 10⁴ copies/mL or \> 2000 IU/mL)
       * Hepatitis C virus (HCV) infection with detectable HCV RNA (\> 1 × 10³ copies/mL)
       * Other hepatitis, cirrhosis.
   20. Active or suspected autoimmune disease (e.g., myasthenia gravis, myositis, autoimmune hepatitis, SLE, RA, inflammatory bowel disease, MS, vasculitis, glomerulonephritis, uveitis, hypophysitis). Exceptions may apply for vitiligo, psoriasis, or thyroiditis that is controlled with replacement therapy.
   21. Any social or medical condition (e.g., alcohol or drug abuse, severe psychiatric illness) that, in the investigator's judgment, could interfere with adherence to study procedures, compromise safety, or lead to premature study discontinuation.

Where this trial is running

Guangzhou

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

Study contacts

• Study coordinator: Zhiqiang Wang

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