QL1706 (Iparomlimab/Tuvonralimab) Plus Lenvatinib With or Without Cryoablation for Advanced Biliary Tract Cancer (CASTLE-ZS-04): a Multicenter, Randomized, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This study will evaluate the efficacy and safety of cryoablation combined with QL1706 (iparomlimab/tuvonralimab) plus lenvatinib in patients with advanced biliary tract cancer (BTC) who have progressed after first-line treatment.
详细描述
This study is a multicenter, open-label, multi-cohort, phase 2 exploratory clinical trial. Subjects enrolled are patients with advanced biliary tract cancer (BTC) who have failed first-line treatment based on chemotherapy combined with immune checkpoint inhibitors. The study evaluates the efficacy and safety of second-line cryoablation combined treatment regimens.
Eligible patients are divided into three independent cohorts according to the primary site of the tumor: intrahepatic cholangiocarcinoma (ICC) cohort, extrahepatic cholangiocarcinoma (ECC) cohort, and gallbladder cancer (GBC) cohort. Within each cohort, patients are randomly assigned 1:1 to the following two treatment groups: Group 01: QL1706 + Lenvatinib, Group 02: QL1706+lenvatinib +Cryoablation. This results in six study cohorts: ICC-01, ICC-02, ECC-01, ECC-02, GBC-01, and GBC-02.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained.
- •Age ≥ 18 years at time of study entry.
- •Participants must have unresectable or metastatic histologically confirmed biliary tract cancer.
- •Participants must have failed 1 line of GemCis plus PD1/PD-L1 inhibitor for advanced cholangiocarcinoma due to disease progression or toxicity.
- •At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
- •Performance status (PS) ≤ 2 (ECOG scale).
- •Life expectancy of at least 12 weeks.
- •Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
- •Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
- •Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.
排除标准
- •History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
- •Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
- •Prior treatment with cryoablation.
- •RFA and resection administered less than 4 weeks prior to study treatment start.
- •Radiotherapy administered less than 4 weeks prior to study treatment start.
- •Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
- •Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
- •Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- •Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
- •Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to: a) history of interstitial lung disease b) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) c) known acute or chronic pancreatitis d) active tuberculosis e) any other active infection (viral, fungal or bacterial) requiring systemic therapy f) history of allogeneic tissue/solid organ transplant g) diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. i) Live vaccine within 30 days prior to the first dose of treatment or during study treatment. j) History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
- •Medication that is known to interfere with any of the agents applied in the trial.
- •Any other efficacious cancer treatment except protocol specified treatment at study start.
- •Patient has received any other investigational product within 28 days of study entry.
- •Prior therapy with an anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
- •Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
研究组 & 干预措施
ECC-02
Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib +cryoablation
干预措施: Lenvatinib (Drug)
ICC-01
Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
ICC-02
Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib+cryoablation
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
ICC-02
Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib+cryoablation
干预措施: Cryoablation (Procedure)
ECC-01
Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
ECC-02
Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib +cryoablation
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
ECC-02
Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib +cryoablation
干预措施: Cryoablation (Procedure)
GBC-01
Gallbladder cancer (GBC) received QL1706 + lenvatinib
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
GBC-02
Gallbladder cancer (GBC) received QL1706 + lenvatinib+cryoablation
干预措施: QL1706 (Iparomlimab/Tuvonralimab) (Drug)
GBC-02
Gallbladder cancer (GBC) received QL1706 + lenvatinib+cryoablation
干预措施: Cryoablation (Procedure)
ICC-01
Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib
干预措施: Lenvatinib (Drug)
GBC-01
Gallbladder cancer (GBC) received QL1706 + lenvatinib
干预措施: Lenvatinib (Drug)
ICC-02
Intrahepatic cholangiocarcinoma (ICC) received QL1706 + lenvatinib+cryoablation
干预措施: Lenvatinib (Drug)
ECC-01
Extrahepatic cholangiocarcinoma (ECC) received QL1706 + lenvatinib
干预措施: Lenvatinib (Drug)
GBC-02
Gallbladder cancer (GBC) received QL1706 + lenvatinib+cryoablation
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 24 months
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
次要结局
- Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(24 months)
- Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(24 months)
- Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(24 months)
- Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(24 months)
- Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(42 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(42 months)
- Translational study(42 months)