QL1706（Iparomlimab/Tuvonralimab) Combined With Gemcitabine and Cisplatin as First-Line Treatment for PD-L1-Positive Biliary Tract Cancer

NCT07733115 | Recruiting Phase 2

• 1 other identifier: QL1706-PDL1+BTC
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancer (BTC)

Keywords

Biliary Tract Cancer; Immunotherapy; Iparomlimab; Gemcitabine; Cisplatin; Tuvonralimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of participants with CR or PR per RECIST 1.1, assessed by investigator

  Up to 24 months

Secondary Outcomes (6)

• Disease Control Rate (DCR)

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 months

• Time to Response (TTR)

  Up to 24 months

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 36 months (or longer as follow-up continues)

Other Outcomes (2)

• AI-Assessed Objective Response Rate (AI-ORR)

  Up to 24 months

• correlation between biomarkers With Treatment Response

  Up to 24 months

Study Arms (1)

QL1706 in Combination With GC First-Line Therapy

EXPERIMENTAL

Participants receive QL1706 (5 mg/kg, IV, once every 3 weeks) in combination with gemcitabine (1000 mg/m², IV, days 1 and 8, every 3 weeks) and cisplatin (25 mg/m², IV, days 1 and 8, every 3 weeks) for up to 8 cycles, followed by QL1706monotherapy maintenance (5 mg/kg, IV, 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.

Biological: Iparomlimab and Tuvonralimab (QL1706); Drug: Gemcitabine and Cisplatin Chemotherapy

Interventions

Iparomlimab and Tuvonralimab (QL1706) BIOLOGICAL

QL1706 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.

QL1706 in Combination With GC First-Line Therapy

Gemcitabine and Cisplatin Chemotherapy DRUG

Gemcitabine 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.

QL1706 in Combination With GC First-Line Therapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first drug administration. Replacement therapies (e.g., levothyroxine, insulin, physiological corticosteroids for adrenal or pituitary insufficiency) are not regarded as systemic treatment. Known primary immunodeficiency. Patients with positive autoantibodies only should be assessed by the investigator for the presence of autoimmune disease.
• Systemic corticosteroid therapy (excluding nasal, inhaled, or other topical corticosteroids) or any other form of immunosuppressive therapy within 4 weeks prior to first dose. Note: Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or equivalent) are permitted.
• Clinically uncontrolled pleural effusion or ascites (patients who do not require drainage or have no significant increase in fluid for 3 days after drainage cessation may be enrolled).
• Known allogeneic organ transplant (except corneal transplant) or allogeneic hematopoietic stem cell transplant.
• Known allergy to any active ingredient or excipient of the study drugs.
• Presence of clinically significant cardiovascular and cerebrovascular diseases, including:
• Electrocardiogram abnormalities (e.g., complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation) that are symptomatic and difficult to control.
• Unstable angina, congestive heart failure, or chronic heart failure of New York Heart Association (NYHA) Class ≥ 2.
• Any arterial thrombotic, embolic, or ischemic event (e.g., myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack) within 6 months prior to enrollment.
• Uncontrolled hypertension (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg).
• Major surgical procedure (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to first dose, or non-healing wounds, ulcers, or fractures.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jian Zhou

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XiaoYong Huang

CONTACT

+86 15021519215; huang.xiaoyong@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: July 29, 2026
• Study Start: July 20, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)