AK104 or AK112 plus TT-00420 for advanced hepatocellular carcinoma

An Open-label, Multicenter, Phase II Clinical Study of AK104/AK112 in Combination With TT-00420 Tablet in Patients With Advanced Hepatocellular Carcinoma.

This study tests whether combining AK104 or AK112 with the oral drug TT-00420 (tinengotinib) can help adults with advanced hepatocellular carcinoma (HCC).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Locations: 1 site (Wuhan, China)
• Trial ID: NCT07052253 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter Phase II study of two investigational biologic agents (AK104 or AK112) given with the oral kinase inhibitor TT-00420 (tinengotinib) in patients with advanced HCC. Eligible participants have measurable disease by RECIST v1.1, BCLC stage C (or stage B not amenable to curative local therapy), Child-Pugh score ≤7, and ECOG performance status 0–1. Cohorts A and B require no prior systemic therapy for HCC; other cohorts may have different prior-treatment rules. The trial will monitor tumor responses and safety to determine whether the combination shows sufficient activity to justify further development.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically or clinically confirmed advanced HCC (BCLC C or unresectable B), at least one measurable lesion, Child-Pugh score ≤7, ECOG 0–1, and clinically controlled HBV or HCV are the ideal candidates.

Not a fit: Patients with fibrolamellar, sarcomatoid, or cholangiocarcinoma histology, recent other malignancies, hepatic encephalopathy, significant uncontrolled cardiac or pericardial disease, or substantially impaired liver function are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could shrink tumors or delay progression and provide a new treatment option for people with advanced HCC.

How similar studies have performed: Combining immune-targeted therapies with targeted oral agents has produced positive results in HCC (for example, immunotherapy plus anti-VEGF), but these specific agents are investigational and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years.
2. Histologically or cytologically confirmed hepatocellular carcinoma, or meets the clinical diagnostic criteria for hepatocellular carcinoma.
3. Barcelona Clinic Liver Cancer (BCLC) stage C; or stage B and assessed by the investigator as unsuitable for curative topical treatment.
4. For cohorts A and B: No prior systemic anti-cancer treatment for hepatocellular carcinoma.
5. At least one measurable lesion according to RECIST v1.1 criteria.
6. Child-Pugh liver function score ≤7. ECOG performance status of 0 or 1.
7. Clinically controllable HBV or HCV infection.
8. Adequate organ and bone marrow function.

Exclusion Criteria:

1. Previous histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.
2. Diagnosed with another malignancy within 3 years.
3. History of hepatic encephalopathy.
4. Presence of clinically significant pericardial effusion; symptomatic pleural effusion requiring drainage or moderate to severe ascites uncontrolled by diuretics.
5. Concurrent infection with HBV and HCV.
6. Presence of central nervous system metastases or meningeal metastases.
7. Esophageal or gastric variceal bleeding within 6 months. Imaging (CT or MRI) shows extrahepatic metastasis invading major blood vessels or indistinct vascular boundaries, with high bleeding risk assessed by the researcher.
8. Liver tumor volume exceeding 50% of total liver volume; portal vein main trunk tumor thrombus or tumor thrombus in contralateral main branch of the portal vein, or mesenteric vein tumor thrombus; presence of inferior vena cava thrombus or involvement of the heart.
9. Received topical treatment for liver cancer, any systemic anti-tumor drugs, or other clinical trial drugs within 4 weeks prior to the first administration.
10. Unable to swallow, or has severe gastrointestinal disease or gastrointestinal dysfunction. History of intestinal obstruction or intestinal perforation within 6 months.
11. Uncontrolled hypertension, symptomatic heart failure, symptomatic or poorly controlled arrhythmia, myocarditis, cardiomyopathy, history of malignant arrhythmias.
12. Participants with severe bleeding tendencies or coagulation disorders.
13. Active pulmonary tuberculosis, active syphilis, or history of HIV infection.
14. Severe infection within 4 weeks prior to the first administration, or received systemic anti-infective treatment within 14 days.
15. Other conditions with high medical risk or secondary tumor symptoms, which, in the judgment of the researcher, make the participant unsuitable for participation in the study.

Where this trial is running

Wuhan, China

• Union Hospital Tongji Medical College Huazhong University of Science And Technology — Wuhan, China, China (Recruiting)

Study contacts

• Study coordinator: Ting Liu, M.D.

Conditions Hepatocellular Carcinoma