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

A Clinical Study of Iparomlimab and Tuvonralimab Combined With Lenvatinib, Radiotherapy, and Hepatic Arterial Infusion Chemotherapy as First-Line Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

The purpose of this study is to learn how well a combination of iparomlimab and tuvonralimab (QL1706), lenvatinib, radiotherapy, and hepatic arterial infusion chemotherapy (HAIC) works and how safe it is for people with hepatocellular carcinoma (HCC) that has grown into the portal vein, forming a portal vein tumor thrombus (PVTT).

Participants will receive iparomlimab and tuvonralimab together with lenvatinib, radiotherapy directed at the portal vein tumor thrombus, and HAIC, which delivers chemotherapy directly through the hepatic artery. Researchers will evaluate how long the cancer remains controlled without getting worse, how much the tumors shrink, how long participants survive, and whether the treatment makes surgery possible for some participants. Treatment-related side effects will also be assessed.

The study will also explore whether features in tumor tissue and blood are associated with treatment response and may help identify patients who are more likely to benefit from this treatment strategy.

Inclusion Criteria:

1. Age ≥18 and ≤75 years at the time of signing informed consent.
2. Histologically or clinically confirmed hepatocellular carcinoma (HCC) according to the 2024 Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer.
3. Radiologically confirmed portal vein tumor thrombus (PVTT), classified as Cheng type I-IV.
4. No prior systemic or local treatment directed at PVTT, including targeted therapy, immunotherapy, or systemic chemotherapy.
5. Child-Pugh class A or B with a Child-Pugh score ≤7.
6. Considered unsuitable for curative surgery or liver transplantation after multidisciplinary evaluation, but suitable for radiotherapy.
7. 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.
8. At least one measurable lesion according to mRECIST.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
10. Life expectancy >3 months.
11. No history of abdominal radiotherapy.
12. 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.
13. Willing and able to comply with study follow-up until death, study completion, or study termination.

Exclusion Criteria:

1. ECOG performance status ≥2.
2. Child-Pugh score ≥8.
3. Severe dysfunction of major organs, including the heart, liver, or kidneys.
4. Prior targeted therapy, immunotherapy, radiotherapy, systemic chemotherapy, or other anticancer treatment.
5. Known hypersensitivity or allergic reaction to any component of the study treatment.
6. History of organ transplantation or autologous/allogeneic stem cell transplantation.
7. Currently receiving chronic systemic immunotherapy or hormonal therapy other than physiologic replacement therapy.
8. 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.
9. Concurrent other malignancy that has not been cured, except carcinoma in situ at another site.
10. 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.
11. 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.
12. Pregnancy or breastfeeding.
13. 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.
14. Lack of legal capacity or limited legal capacity.
15. Other contraindications to radiotherapy or targeted/immunotherapy.
16. Any participant considered unsuitable for enrollment by the investigator.