A Phase II Clinical Study of AK104/AK112 in Combination With TT-00420 Tablet for Advanced HCC.

Not Applicable

Not yet recruiting

• Conditions: Hepatocellular Carcinoma (HCC)
• Interventions: Drug: TT-00420 (tinengotinib); Drug: AK104; Drug: AK112

• Registration Number: NCT07052253
• Lead Sponsor: Akeso

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-26
• Study First Submitted QC: 2025-06-26
• Last Update Submitted: 2025-06-26
• Study First Posted: 2025-07-04
• Last Update Posted: 2025-07-04
• Study Start: 2025-07-25
• Primary Completion: 2027-05-10
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1（Safety Lead-In Phase）	TT-00420 (tinengotinib)	AK104 10mg/kg Q3W+TT-00420 10mg PO QD （n=3-6）
Cohort 1（Safety Lead-In Phase）	AK104	AK104 10mg/kg Q3W+TT-00420 10mg PO QD （n=3-6）
Cohort 2（Safety Lead-In Phase）	TT-00420 (tinengotinib)	AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=3-6）
Cohort 2（Safety Lead-In Phase）	AK112	AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=3-6）
Cohort A（Expansion Cohort Phase）	TT-00420 (tinengotinib)	AK104 10mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）
Cohort A（Expansion Cohort Phase）	AK104	AK104 10mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）
Cohort B（Expansion Cohort Phase）	TT-00420 (tinengotinib)	AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）
Cohort B（Expansion Cohort Phase）	AK112	AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）
Cohort C（Expansion Cohort Phase）	TT-00420 (tinengotinib)	TT-00420 10mg PO QD（n=20-30）

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 2 years	assessed by investigator per RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	up to 2 years	assessed by investigator per RECIST v1.1
Disease control rate(DCR)	Up to 2 years	assessed by investigator per RECIST v1.1
Duration of Response (DOR)	Up to 2 years	assessed by investigator per RECIST v1.1
Time to Response (TTR)	Up to 2 years	assessed by investigator per RECIST v1.1
Time to Progression (TTP)	Up to 2 years	assessed by investigator per RECIST v1.1
Overall Survival(OS)	Up to 2 years	OS is defined as the time from randomization or first dosing to death due to any cause.

Trial Locations

Locations (1)

Union Hospital Tongji Medical College Huazhong University of Science And Technology; 🇨🇳 Wuhan, China