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

Akeso

Status and phase: Enrolling; Phase 2

Conditions: Hepatocellular Carcinoma (HCC)

Treatments: Drug: TT-00420 (tinengotinib); Drug: AK104; Drug: AK112

Study type: Interventional

Funder types: Industry

Identifiers

NCT07052253

AK104-223

Details and patient eligibility

About

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

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 5 patient groups

Cohort 1（Safety Lead-In Phase）

Experimental group

Description:

AK104 10mg/kg Q3W+TT-00420 10mg PO QD （n=3-6）

Treatment:

Drug: AK104

Drug: TT-00420 (tinengotinib)

Cohort 2（Safety Lead-In Phase）

Experimental group

Description:

AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=3-6）

Treatment:

Drug: AK112

Drug: TT-00420 (tinengotinib)

Cohort A（Expansion Cohort Phase）

Experimental group

Description:

AK104 10mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）

Treatment:

Drug: AK104

Drug: TT-00420 (tinengotinib)

Cohort B（Expansion Cohort Phase）

Experimental group

Description:

AK112 20mg/kg Q3W + TT-00420 10mg PO QD（n=20-30）

Treatment:

Drug: AK112

Drug: TT-00420 (tinengotinib)

Cohort C（Expansion Cohort Phase）

Experimental group

Description:

TT-00420 10mg PO QD（n=20-30）

Treatment:

Drug: TT-00420 (tinengotinib)