A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma

An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma

An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for patients with advanced hepatocellular carcinoma.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: AK104; Drug: Lenvatinib

Detailed Description

This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104 plus lenvatinib for the treatment of advanced hepatocellular carcinoma.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Chinese PLA General 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.
• BCLC stage C, and non-resectable BCLC stage B .
• At least one measurable lesion according to RECIST criteria.
• ECOG of 0 or 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.
• History of hepatic encephalopathy or liver transplantation.
• Clinical significance of hydrothorax, ascites or pericardial effusion.
• Central nervous system metastases and/or carcinomatous meningitis.
• 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.
• Tumor volume > 50% liver volume; portal vein tumor thrombus or inferior vena cava tumor thrombus.
• Inadequately controlled arterial 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 and Lenvatinib; AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD	Biological: AK104; Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months; Drug: Lenvatinib; Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

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
Progression-free survival (PFS)	Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.	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
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 of AK104 and
Observed concentrations of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of AK104 through 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).	From first dose of AK104 through 90 days after last dose of AK104

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Akeso Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Shunchang Jiao, MD, Chinese PLA General Hospital; Principal Investigator: Li Bai, MD, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: June 21, 2020
• First Submitted That Met QC Criteria: June 21, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Anti-PD-1; Tyrosine Kinase Inhibitor (TKI); Anti-CTLA-4
• 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: AK104-206

Drug and device information, study documents

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