A Study of AK112 in Patients With Unresectable Hepatocellular Carcinoma (HCC)

A Phase II Study of AK112 (PD-1/VEGF Bispecific) in Patients With Unresectable Hepatocellular Carcinoma (HCC)

Phase II open label, multicenter study to evaluate the efficacy and safety of AK112 (PD-1/VEGF Bispecific) in patients with unresectable hepatocellular carcinoma (HCC).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: AK112

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Provincial Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• 18 to 75 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have a life expectancy of at least 3 months.
• BCLC stage B or C, not amenable to curative surgery.
• Hepatocellular carcinoma confirmed by histology/cytology. Cirrhosis meets the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Diagnosis of Liver Diseases (AASLD).
• At least one measurable untreated lesion.
• Child-Pugh class A.
• Has adequate organ function.
• All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

• With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues.
• History of malignancy other than HCC within 5 years, except that basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Have a history of hepatic encephalopathy or have a history of liver transplantation.
• With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion.
• Central nervous system (CNS) metastasis or meningeal metastasis.
• Prior immunotherapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• Prior systemic bevacizumab and its analogues treatment.
• Severe bleeding tendency or coagulation dysfunction; occurred arteriovenous thromboembolic events or bleeding events due to esophageal and/or gastric varices within 6 months before the first administration.
• Known presence or history of required hormone treatment interstitial lung disease or non-infectious pneumonitis.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has undergone major surgery within 30 days prior to the first dose of study treatment.
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects receive AK112 on Day 1 of every 3-week cycle (Q3W) until progression.	Drug: AK112; IV infusion, specified dose on specified days
Experimental: Cohort 2; Subjects receive AK112 on Day 1 of every 3-week cycle (Q3W) until progression.	Drug: AK112; IV infusion, specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with Adverse Events (AEs)	Up to approximately 2 years
Objective Response Rate (ORR) Per RECIST v1.1	Up to approximately 2 years
Objective Response Rate (ORR) Per mRECIST	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to approximately 2 years
Disease control rate (DCR)	Up to approximately 2 years
Time to response (TTR)	Up to approximately 2 years
Progression free survival (PFS)	Up to approximately 2 years
Duration of Response (DoR)	Up to approximately 2 years

Other Outcome Measures

Outcome Measure	Time Frame
Percentage of participants who obtain R0 resection	Up to approximately 2 years
Percentage of participants who obtain a major pathologic responses (MPR)	Up to approximately 2 years
Percentage of participants who obtain a pathologic complete response (pCR)	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Jingfeng Liu, Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): June 14, 2025

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: AK112-207

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No