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).
Histologically or cytologically confirmed diagnosis of tumors containing components other than biliary adenocarcinoma (e.g., neuroendocrine carcinoma, squamous cell carcinoma, or mixed histologies).
Prior treatment with anti-PD-1/PD-L1 agents, anti-CTLA-4 agents, or other antitumor immunotherapies.
Presence of unresolved Grade >1 toxicities related to any previous antitumor therapy (persistent Grade 2 alopecia, fatigue, or endocrine disorders well-controlled with hormone replacement therapy are excluded).
History of other malignancies within 5 years prior to enrollment, except for radically cured basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ with no evidence of recurrence, or other malignancies with complete remission and no active disease for at least 2 years prior to enrollment.
Single group
Iparomlimab and Tuvonralimab (QL1706)
Biological/VaccineQL1706 is a bifunctional combination antibody composed of a PD-1 monoclonal antibody (IgG4 isotype, no ADCC effect) and a CTLA-4 monoclonal antibody (IgG1 isotype, with ADCC effect, engineered with R255K mutation to shorten half-life and reduce toxicity). It is administered at 5 mg/kg via intravenous infusion once every 3 weeks.
Gemcitabine and Cisplatin Chemotherapy
DrugGemcitabine is a nucleoside analog antimetabolite antineoplastic agent, and cisplatin is a platinum-based alkylating agent. The combination is administered as follows: gemcitabine 1000 mg/m² and cisplatin 25 mg/m² via intravenous infusion on days 1 and 8 of each 21-day cycle, for up to 8 cycles.
Objective Response Rate (ORR)
Proportion of participants with CR or PR per RECIST 1.1, assessed by investigator
Disease Control Rate (DCR)
DCR is defined as the proportion of participants achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 criteria, as assessed by the investigator.
Duration of Response (DOR)
DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death due to any cause, whichever occurs first.
Time to Response (TTR)
TTR is defined as the time from enrollment to the first documented objective response (CR or PR).
Progression-Free Survival (PFS)
PFS is defined as the time from enrollment to the first documented radiographic disease progression or death due to any cause, whichever occurs first.
AI-Assessed Objective Response Rate (AI-ORR)
AI-ORR is defined as the proportion of participants achieving a best overall response of CR or PR per RECIST 1.1 criteria, as assessed by artificial intelligence (AI) imaging
correlation between biomarkers With Treatment Response
To evaluate the correlation between tumor tissue or blood-based biomarkers and treatment efficacy
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