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

Akeso1 site in 1 country59 target enrollmentJuly 7, 2020

ConditionsHepatocellular Carcinoma

InterventionsAK104 Lenvatinib

DrugsLenvatinib

Overview

Phase: Phase 1
Intervention: AK104
Conditions: Hepatocellular Carcinoma
Sponsor: Akeso
Enrollment: 59
Locations: 1
Primary Endpoint: Objective response rate (ORR)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

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.

Registry

clinicaltrials.gov

Start Date

July 7, 2020

End Date

November 20, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Akeso

Responsible Party

Sponsor

Eligibility Criteria

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
•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.

Arms & Interventions

AK104 and Lenvatinib

AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight\<60kg,PO QD

Intervention: AK104

AK104 and Lenvatinib

AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight\<60kg,PO QD

Intervention: Lenvatinib

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: Up to 2 years

ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.

Secondary Outcomes

Progression-free survival (PFS)(Up to 2 years)
Duration of response (DoR)(Up to 2 years)
Disease control rate (DCR)(Up to 2 years)
Number of participants with adverse events (AEs)(the time of informed consent signed through 90 days after the last dose of AK104 and)
Observed concentrations of AK104(From first dose of AK104 through 90 days after last dose of AK104)
Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK104 through 90 days after last dose of AK104)