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

Sponsor

Akeso (Industry)

Overall Status

Unknown status

CT.gov ID

NCT04444167

Collaborator

Akeso Pharmaceuticals, Inc. (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Biological: AK104 Drug: Lenvatinib	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 30, 2020

Anticipated Primary Completion Date :

Jan 30, 2022

Anticipated Study Completion Date :

Mar 31, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [Up to 2 years]
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.

Secondary Outcome Measures

Disease control rate (DCR) [Up to 2 years]
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.
Duration of response (DoR) [Up to 2 years]
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
Progression-free survival (PFS) [Up to 2 years]
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.
Number of participants with adverse events (AEs) [the time of informed consent signed through 90 days after the last dose of AK104 and]
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.
Observed concentrations of AK104 [From first dose of AK104 through 90 days after last dose of AK104]
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Number of subjects who develop detectable anti-drug antibodies (ADAs) [From first dose of AK104 through 90 days after last dose of AK104]
The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.