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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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 ≥
- •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.
- •Active tuberculosis; patients currently receiving anti-tuberculosis treatment or those who received anti-tuberculosis therapy within 1 year before the first drug administration.
- •Active or uncontrolled infection requiring systemic treatment.
- •Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction.
- •Poorly controlled diabetes (fasting blood glucose > 10 mmol/L).
- •Urinalysis showing protein ≥ 2+ with 24-hour urine protein > 1.0 g.
- •Confirmed HIV positivity or history of acquired immunodeficiency syndrome (AIDS).
- •Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copy number > 2000 IU/mL); patients with HBV-DNA positive may be enrolled if levels show a declining trend.
- •Active HCV infection (HCV antibody positive and HCV-RNA above the lower limit of detection).
- •Vaccination with live attenuated vaccine within 4 weeks prior to first dose.
- •Pregnant or breastfeeding females, or females planning to become pregnant before drug administration, during treatment or within 6 months after the last dose of study drug.
- •Psychiatric disorders preventing treatment compliance.
- •Any concomitant disease, prior treatment, abnormal laboratory findings, history of substance abuse or current substance use, which in the investigator's judgment may compromise patient safety, hinder informed consent acquisition, affect treatment compliance or interfere with the safety assessment of the study drug.
研究组 & 干预措施
QL1706 in Combination With GC First-Line Therapy
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.
干预措施: Gemcitabine and Cisplatin Chemotherapy (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 24 months
Proportion of participants with CR or PR per RECIST 1.1, assessed by investigator
次要结局
- 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))
- Safety(Up to 30 days after last dose for AEs; up to 90 days after last dose for SAEs and irAEs)
研究者
Jian Zhou
Professor
Shanghai Zhongshan Hospital