A Phase II Study of AK104 Plus Lenvatinib and TACE in HCC

An Open Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of AK104 Plus Lenvatinib and TACE in the Treatment of Unresectable, Non-metastatic Hepatocellular Carcinoma

To evaluate the efficacy and safety of AK104 plus lenvatinib combined with on-demand TACE in participants with unresectable, non-metastatic hepatocellular carcinoma

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable, Non-metastatic Hepatocellular Carcinoma
• Intervention / Treatment: Biological: AK104; Drug: Lenvatinib; Procedure: TACE

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • The First Hospital of Beijing University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong 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:

• Signed written informed consent form voluntarily.
• Histologically or cytologically documented hepatocellular carcinoma.
• CNLC IIa IIb or IIIa
• The main portal vein was not completely obstructed,
• Child-Pugh A or B
• At least one measurable lesion according to RECIST criteria
• ECOG PS 0-1
• 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
• For HCC lesions ≥ 10 cm in any dimension, imaging evaluation showed that there were more than 10 lesions
• The main portal vein and the left and right primary branches were clogged with cancer thrombus
• History of hepatic encephalopathy or liver transplantation
• 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.
• Inadequately controlled 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104+Lenvatinib+TACE; Participants will receive AK104 IV every 3 weeks (Q3W) and Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD The first Transarterial chemoembolization will be performed at the beginning of study.	Biological: AK104; Subjects will receive AK104 until disease progression or for a maximum of 24 months; Drug: Lenvatinib; Subjects will receive lenvatinib until disease progression or for a maximum of 24 months; Procedure: TACE; On demand TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, which ever occurs first.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.	Up to 2 years
Duration of response (DoR)	Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first	Up to 2 years
Objective response rate (ORR	ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.	Up to 2 years
Number of participants with adverse events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	the time of informed consent signed through 90 days after the last dose

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Guoliang Shao, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

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; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: AK104-216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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