A Study of AK104+Lenvatinib in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma

A Phase III, Randomized, Double-blinded, Multicenter Study of Cadonilimab (AK104) + Lenvatinib in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma

A study to evaluate cadonilimab (AK104) + lenvatinib in combination with transarterial chemoembolization (TACE) versus TACE in participants with incurable/non-metastatic hepatocellular carcinoma

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: AK104; Procedure: TACE; Other: Placebo for AK104; Other: Placebo for Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 469
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86 (0760) 8987 3999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450004
      • Henan Cancer Hospital
      • Contact: Hailiang Li
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
      • Contact: Shanzhi Gu
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
      • Contact: Gaojun Teng
  • Shanxi
    • Taiyuan, Shanxi, China, 030009
      • Shanxi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital
      • Contact: Guoliang Shao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a diagnosis of HCC confirmed by histology/cytology，or meet the clinical diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD)
2. No evidence of metastasis
3. Not amenable to curative surgery or transplantation or curative ablation but amenable to TACE
4. Child Pugh score class A
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
6. Measurable disease by RECIST 1.1
7. Adequate organ function

Exclusion Criteria:

1. History of liver transplantation
2. History of hepatic encephalopathy
3. Uncontrolled arterial hypertension
4. Deep venous thrombosis within 3 months before first treatment
5. Bleeding events within the last 6 months
6. Co-infection with HBV and HCV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; AK104+ Lenvatinib in Combination With Transarterial Chemoembolization (TACE)	Drug: Lenvatinib; oral; Drug: AK104; intravenous; Procedure: TACE; TACE (chemo and embolic agent injection into the hepatic artery)
Placebo Comparator: Arm B; Placebo for AK104 + Placebo for Lenvatinib in Combination With TACE	Procedure: TACE; TACE (chemo and embolic agent injection into the hepatic artery); Other: Placebo for AK104; intravenous; Other: Placebo for Lenvatinib; oral
Other: Arm C; AK104 + Placebo for Lenvatinib in Combination With TACE	Drug: AK104; intravenous; Procedure: TACE; TACE (chemo and embolic agent injection into the hepatic artery); Other: Placebo for Lenvatinib; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR).	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 2 years
PFS per RECIST 1.1	Assessed by investigators	Up to approximately 2 years
Objective Response Rate (ORR) per RECIST 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	Assessed by BICR and investigators	Up to approximately 2 years
Duration of Response (DOR) per RECIST 1.1 and mRECIST	Assessed by BICR and investigators	Up to approximately 2 years
Disease Control Rate (DCR) per RECIST 1.1 and mRECIST	Assessed by BICR and investigators	Up to approximately 2 years
Time to Response (TTR) per RECIST 1.1 and mRECIST	Assessed by BICR and investigators	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Gaojun Teng, MD, Zhongda Hospital; Principal Investigator: Guoliang Shao, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 2, 2024
• Primary Completion (Estimated): October 25, 2025
• Study Completion (Estimated): May 23, 2026

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: AK104-308

Drug and device information, study documents

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