A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma

An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma

An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma.

This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 plus lenvatinib for the treatment of advanced hepatocellular carcinoma.

Inclusion Criteria:

• Signed written informed consent form voluntarily.
• Histologically or cytologically documented hepatocellular carcinoma.
• BCLC stage C, and non-resectable BCLC stage B .
• At least one measurable lesion according to RECIST criteria.
• ECOG of 0 or 1.
• Adequate organ function.
• Estimated life expectancy of ≥3 months.
• For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent.

Exclusion Criteria:

• Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
• History of hepatic encephalopathy or liver transplantation.
• Clinical significance of hydrothorax, ascites or pericardial effusion.
• Central nervous system metastases and/or carcinomatous meningitis.
• Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under thrombolytic therapy.
• Occurred arteriovenous thromboembolic events within 6 months before the first administration.
• Tumor volume > 50% liver volume; portal vein tumor thrombus or inferior vena cava tumor thrombus.
• Inadequately controlled arterial hypertension.
• Attack of symptomatic congestive heart failure (LVEF<50%); History of congenital long QT syndrome.
• Known presence or history of interstitial lung disease or required hormone treatment interstitial lung disease.
• Severe infections.
• Receipt of any anti-tumor treatment, chemotherapy, targeted therapy, immunotherapy,
• Enrollment of another clinical study within 4 weeks prior to the first administration of study drugs.
• Unable to receive an enhanced CT or MRI scan of the liver.