Iparomlimab and Tuvonralimab With Lenvatinib, Radiotherapy, and HAIC for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Prior treatment

• Prior targeted therapy, immunotherapy, radiotherapy, systemic chemotherapy, or other anticancer treatment.
• Currently receiving chronic systemic immunotherapy or hormonal therapy other than physiologic replacement therapy.
• Any unstable systemic disease, including active infection; uncontrolled severe hypertension; unstable angina; new-onset angina within the previous 3 months; congestive heart failure of NYHA class II or higher; myocardial infarction within the previous 6 months; severe cardiac arrhythmia requiring medication; gastrointestinal bleeding within the previous 1 month; or active bleeding tendency.
• Concurrent other malignancy that has not been cured, except carcinoma in situ at another site.
• Other contraindications to radiotherapy or targeted/immunotherapy.

Other illness

• Severe dysfunction of major organs, including the heart, liver, or kidneys.
• Known hypersensitivity or allergic reaction to any component of the study treatment.
• History of organ transplantation or autologous/allogeneic stem cell transplantation.
• Evidence of acute or active hepatitis B or hepatitis C infection, including HBV-DNA \>2,000 IU/mL or HCV-RNA \>1,000 copies/mL.
• Any other unfavorable medical or psychiatric condition that, in the investigator's judgment, may affect protocol compliance or evaluation of study endpoints and makes the participant unsuitable for the study.

Lab values

• Any disease, metabolic disorder, physical examination finding, or laboratory abnormality that, in the investigator's judgment, suggests a contraindication to the study treatment or a high risk of treatment-related complications.

Other

• ECOG performance status ≥2.
• Child-Pugh score ≥8.
• Pregnancy or breastfeeding.
• Lack of legal capacity or limited legal capacity.
• Any participant considered unsuitable for enrollment by the investigator.

• Age ≥18 and ≤75 years at the time of signing informed consent.
• Histologically or clinically confirmed hepatocellular carcinoma (HCC) according to the 2024 Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer.
• Radiologically confirmed portal vein tumor thrombus (PVTT), classified as Cheng type I-IV.
• No prior systemic or local treatment directed at PVTT, including targeted therapy, immunotherapy, or systemic chemotherapy.
• Child-Pugh class A or B with a Child-Pugh score ≤7.
• Considered unsuitable for curative surgery or liver transplantation after multidisciplinary evaluation, but suitable for radiotherapy.
• Adequate organ function, including: WBC ≥3.0 × 10⁹/L; PLT ≥50 × 10⁹/L; hemoglobin ≥80 g/L; ALT ≤5 × ULN; AST ≤5 × ULN; total bilirubin ≤3 × ULN; albumin ≥28 g/L; and creatinine clearance ≥80 mL/min.
• At least one measurable lesion according to mRECIST.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy \>3 months.
• No history of abdominal radiotherapy.
• Women of childbearing potential must use effective contraception beginning at least 1 month before screening and throughout the study until the protocol-specified period after study completion.
• Willing and able to comply with study follow-up until death, study completion, or study termination.