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.
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);
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;
Single group
Iparomlimab and Tuvonralimab Injection (QL1706)
DrugIparomlimab and Tuvonralimab Injection (QL1706)will be administered at a dose of 7.5 mg/kg via intravenous infusion (no premedication required). Each infusion shall last for 30 minutes (no less than 20 minutes and no more than 60 minutes), with an administration interval of 3 weeks, and one treatment cycle is defined as 3 weeks. The maximum cumulative treatment duration shall be 2 years. The administration window for QL1706 is within 7 days after hepatic arterial infusion chemotherapy. If the administration is delayed beyond the scheduled time, the dose for this cycle will be omitted, and the subsequent administration will be resumed at the original dose in accordance with the next scheduled time.
Bevacizumab
DrugBevacizumab will be administered at a dose of 15 mg/kg via intravenous infusion (no premedication required), once every 3 weeks, with one treatment cycle defined as 3 weeks. The maximum cumulative treatment duration shall be 2 years.
Hepatic Arterial Infusion Chemotherapy with Raltitrexed and Oxaliplatin (RALOX-HAIC)
Procedure/SurgeryRALOX regimen chemotherapy will be delivered via hepatic arterial infusion (HAIC). The procedure will be performed using the Seldinger technique for femoral artery puncture and catheterization. Digital subtraction angiography (DSA) will be conducted to identify the blood supply artery of the lesion. A conventional catheter (or a microcatheter if necessary) will be superselectively inserted into the tumor-feeding artery via the celiac trunk or superior mesenteric artery, then the catheter will be retained in the catheter sheath and fixed to the body surface before the patient is returned to the ward. In the ward, the catheter will be connected to an infusion pump for continuous infusion of the following chemotherapeutic agents: Oxaliplatin 85 mg/m² over 2 to 4 hours, and Raltitrexed 3 mg/m² over 1 to 2 hours. The catheter will be removed upon completion of chemotherapy, followed by compression bandaging for hemostasis for 6 hours.
Progression free survival time (PFS)
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
Objective response rate (ORR)
The disease control rate (DCR)
Overall survival time (OS)
Treatment-Emergent Adverse Events (Safety and Tolerability)
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