Iparomlimab and Tuvonralimab (QL1706) With Bevacizumab and RALOX Hepatic Arterial Infusion Chemotherapy for Hepatocellular Carcinoma (HCC) With Vp3/4 Portain Vein Thrombosis : A Prospective, Multicenter, Phase II Study
概览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Progression free survival time (PFS)
概览
简要总结
The goal of this prospective, single-arm, multi-center Phase II clinical trial is to evaluate the clinical efficacy and safety of QL1706 combined with bevacizumab and RALOX hepatic artery infusion chemotherapy in treating liver cancer patients with VP3/4 portal vein tumor thrombus. It will also explore molecular biomarkers that predict the efficacy of this combined therapy.
The main questions it aims to answer are:
What is the progression-free survival (PFS) of patients treated with this regimen? What are the objective response rate (ORR), disease control rate (DCR), and overall survival (OS) of these patients? What is the safety and tolerability profile of this combined treatment? Which molecular biomarkers can predict the efficacy of this therapy? Eligible subjects (who have signed informed consent) will receive RALOX hepatic artery infusion chemotherapy plus QL1706 (7.5mg, intravenous infusion every 3 weeks) and bevacizumab (15mg/kg, intravenous infusion every 3 weeks), with 3 weeks as one treatment cycle. Treatment will continue until a protocol-specified discontinuation event occurs. After treatment, subjects will undergo post-treatment safety follow-up and survival follow-up; those who discontinue treatment for reasons other than disease progression or death will also have tumor progression follow-up.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form;
- •Aged ≥ 18 years, male and female subjects are both eligible;
- •Clinically or pathologically confirmed hepatocellular carcinoma (HCC), with no prior systemic anti-tumor therapy for HCC (including but not limited to molecular targeted therapy, systemic chemotherapy, immunotherapy such as anti-PD-1/PD-L1/CTLA-4 monoclonal antibodies, etc.);
- •Complicated with Type VP3 or VP4 portal vein tumor thrombosis (PVTT);
- •Confirmed to have at least one measurable target lesion by imaging examination during the screening period in accordance with RECIST v1.1 criteria. The measurable lesions should not have received local treatment such as radiotherapy (lesions within the area of previous local treatment can also be selected as target lesions if disease progression is confirmed);
- •Child-Pugh score ≤ 7 points (Child-Pugh class A-B);
- •The maximum diameter of liver tumor ≥ 7 cm;
- •ECOG performance status 0 to 1;
- •Expected survival time ≥ 12 weeks;
- •Function of vital organs meeting the following requirements:
排除标准
- •Histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocellular carcinoma, mixed hepatocellular carcinoma, etc.;
- •Active autoimmune disease, or a history of autoimmune disease with potential for recurrence (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[patients whose condition is controllable only with hormone replacement therapy are not excluded\]); Note: Patients with dermatological diseases that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia), type 1 diabetes with good glycemic control under insulin therapy, or asthma that achieved complete remission in childhood and requires no intervention in adulthood are eligible for enrollment; patients with asthma requiring medical intervention with bronchodilators are ineligible.
- •Administration of immunosuppressants or systemic hormonal therapy for immunosuppressive purposes within 2 weeks prior to the first study medication (dose \> 10 mg/day prednisone or an equivalent dose of other hormones);
- •Current interstitial pneumonia or interstitial lung disease, a history of interstitial pneumonia or interstitial lung disease requiring hormonal therapy, or other pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia that may interfere with the judgment and management of immune-related pulmonary toxicity; patients with evidence of active pneumonia on screening CT or severe impairment of pulmonary function are excluded. Radiation pneumonitis within the radiation field is permitted;
- •Confirmed active pulmonary tuberculosis. For subjects with suspected active pulmonary tuberculosis, a definitive diagnosis shall be made based on chest imaging, sputum examination, and clinical symptoms and signs;
- •Known hypersensitivity to the active ingredients or excipients of the study drugs, or a history of severe hypersensitivity to any other monoclonal antibody or anti-angiogenic targeted drugs;
- •Known history of central nervous system (CNS) metastasis or hepatic encephalopathy;
- •A history of allogeneic stem cell transplantation or solid organ transplantation;
- •Moderate to severe ascites with clinical symptoms requiring therapeutic paracentesis or drainage (except for patients with only a small amount of ascites shown by imaging without clinical symptoms), or uncontrolled moderate to large pleural effusion or pericardial effusion;
- •Severe cardiovascular and cerebrovascular diseases, including but not limited to:
研究组 & 干预措施
Iparomlimab and Tuvonralimab Injection (QL1706) combined with Bevacizumab plus RALOX-HAIC
干预措施: Iparomlimab and Tuvonralimab Injection (QL1706) (Drug)
Iparomlimab and Tuvonralimab Injection (QL1706) combined with Bevacizumab plus RALOX-HAIC
干预措施: Bevacizumab (Drug)
Iparomlimab and Tuvonralimab Injection (QL1706) combined with Bevacizumab plus RALOX-HAIC
干预措施: Hepatic Arterial Infusion Chemotherapy with Raltitrexed and Oxaliplatin (RALOX-HAIC) (Procedure)
结局指标
主要结局
Progression free survival time (PFS)
时间窗: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 2 years)
The progression free survival time defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1
次要结局
- Objective response rate (ORR)(From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 2 years))
- The disease control rate (DCR)(From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 2 years))
- Overall survival time (OS)(From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 2 years))
- Treatment-Emergent Adverse Events (Safety and Tolerability)(Throughout the entire treatment period and 30 days after the last dose)