A Multicenter, Single-Arm, Phase II Clinical Study of QL1706 in Combination With Gemcitabine and Cisplatin (GC) as First-Line Treatment for PD-L1-Positive Biliary Tract Cancer
The goal of this clinical trial is to evaluate whether QL1706(Iparomlimab/Tuvonralimab) in combination with gemcitabine and cisplatin (GC) is effective and safe as a first-line treatment for patients with advanced biliary tract cancer whose tumors are PD-L1 positive (CPS ≥ 1). This is a multicenter, single-arm, phase II clinical study. A total of 38 eligible patients will be enrolled . The main questions it aims to answer are: what proportion of patients achieve objective response (tumor shrinkage) after receiving QL1706 plus GC, as measured by the objective response rate (ORR)? How long do the treatment benefits last, in terms of disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and overall survival (OS)? What is the safety profile of QL1706 combined with GC, including the frequency and severity of adverse events, treatment-related adverse events, serious adverse events, and immune-related adverse events? Participants will receive QL1706 (5 mg/kg, intravenous infusion) once every 3 weeks in combination with gemcitabine (1000 mg/m² on days 1 and 8) and cisplatin (25 mg/m² on days 1 and 8) for up to 8 cycles (each cycle is 3 weeks), and after completing 8 cycles of combination therapy, they will continue QL1706 alone as maintenance therapy (5 mg/kg once every 3 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, death, or completion of 2 years of treatment, whichever occurs first. Participants will undergo tumor imaging assessments (using CT or MRI) every 9 weeks (±7 days) during the treatment period, with responses evaluated . Participants will also have regular blood tests, physical examinations, electrocardiograms, and other safety assessments at each treatment cycle, and will provide tumor tissue and blood samples before treatment and at various time points during the study for biomarker analyses to explore correlations with treatment response. Finally, participants will be followed for adverse events for 30 days after the last dose, for serious adverse events for 90 days after the last dose, and for survival status every 90 days (±14 days) after the end of treatment until death, study completion, or loss to follow-up. The study is expected to provide valuable evidence on whether the addition of QL1706 to standard GC chemotherapy offers a new treatment option for patients with PD-L1-positive advanced biliary tract cancer, and to identify potential biomarkers that may help predict which patients are most likely to benefit from this combination therapy.
• Have signed the written informed consent form and be able to comply with all scheduled visits and study procedures specified in the protocol.
• Aged between 18 and 75 years old (inclusive), with no restriction on gender.
• Histologically confirmed unresectable or metastatic advanced biliary tract adenocarcinoma, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
• PD-L1-positive tumor (Combined Positive Score \[CPS\] ≥ 1).
• Have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
• No prior systemic therapy (chemotherapy, targeted therapy, or immunotherapy). Patients who relapse more than 6 months after curative surgery, and if they have received adjuvant therapy (chemotherapy and/or radiotherapy), relapse more than 6 months after completion of adjuvant therapy, are eligible.
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Have adequate organ and bone marrow function. Laboratory test results obtained within 7 days prior to enrollment shall meet the following requirements. No blood products, erythropoietin, colony-stimulating factors, thrombopoietin, albumin or other parenteral corrective medications are allowed within 14 days before laboratory testing:
‣ Hematology: Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; Platelet (PLT) count ≥ 100×10⁹/L; Hemoglobin (HGB) \> 9 g/dL.
⁃ Liver function: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN.
⁃ Renal function: Creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min.
⁃ Thyroid function: Thyroid-stimulating hormone (TSH) within normal range. If baseline TSH is outside normal range, patients are eligible if total T3 (or FT3) and FT4 are within normal limits.
⁃ Cardiac enzymes: Within normal limits (isolated laboratory abnormalities deemed clinically insignificant by the investigator are allowed).
⁃ Female participants of childbearing potential and male participants whose partners are of childbearing potential must agree to use effective contraception throughout the treatment period and for 6 months after the last study drug administration.