A Phase II Study of AK104 Combination With Lenvatinib Versus Lenvatinib for Second-line HCC

NCT06984718 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: AK104-225
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase II, randomized, open-label, global, multi-center study to compare the efficacy and safety of AK104 in combination with lenvatinib versus lenvatinib in patients with advanced hepatocellular carcinoma who have progressed on the first line treatment of atezolizumab and bevacizumab.

Conditions

HCC; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) per RECIST v1.1 by Blinded Independent Central Review (BICR)

  Proportion of subjects who have a complete or partial response relative to baseline as assessed by BICR according to RECIST v1.1.

  Up to 24 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to 24 months

• Progression-free survival (PFS) assessed by investigator per RECIST v1.1

  Up to 24 months

• Duration of Response (DOR) assessed by investigator per RECIST v1.1

  Up to 24 months

• Time to Response (TTR) assessed by investigator per RECIST v1.1

  Up to 24 months

• Number of participants with adverse event (AE)

  Up to 24 months

Study Arms (2)

AK104+lenvatinib

EXPERIMENTAL

AK104 IV plus lenvatinib orally

Biological: AK104+lenvatinib

lenvatinib

ACTIVE COMPARATOR

lenvatinib orally

Drug: lenvatinib

Interventions

AK104+lenvatinib BIOLOGICAL

Subjects will receive AK104+lenvatinib until disease progression

AK104+lenvatinib

lenvatinib DRUG

Subjects will receive lenvatinib until disease progression

lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the Informed Consent Form (ICF) voluntarily.
• Age ≥18 years at time of signing ICF.
• Histologic or cytologic confirmation of HCC, or clinical diagnosis of HCC as per AASLD criteria.
• BCLC stage B or C, and not suitable for curative surgical or local therapy.
• Participants have progressed on the prior first-line systemic treatment with atezolizumab plus bevacizumab combination treatment.
• At least one measurable lesion according to RECIST v1.1.
• Child-Pugh Class A .
• ECOG performance status of 0 or 1.
• With a life expectancy of ≥3 months.
• Adequate organ and hematologic function.

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Tumor thrombus invasion of superior mesenteric vein.
• Has a known history of, or any evidence of CNS metastases.
• Has received anti-cancer therapy for HCC within 3 weeks prior to the first dose of study treatment.
• Has received systemic anti-cancer therapy other than atezolizumab and bevacizumab.
• Has participated in another clinical study within 4 weeks prior to the first dose.
• History of liver transplantation.
• History of hepatic encephalopathy.
• Clinically symptomatic or recurrently drained pleural effusion, pericardial effusion, or ascites.
• History of bleeding event due to esophageal and/or gastric varices within 6 months prior to the first dose of study treatment.

Sponsors & Collaborators

• Akeso: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Richard S. Finn, Ph.D.

  Department of Medicine, University of California

  PRINCIPAL INVESTIGATOR

• Jian Zhou, Ph.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ting Liu, M.D.

CONTACT

(0760)89873999; clinicaltrials@akesobio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 22, 2025
• Study Start: June 25, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share