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

Primary Purpose

Hepatocellular Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

AK104

Lenvatinib

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Anti-CTLA-4

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AK104 and Lenvatinib

Arm Description

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

Outcomes

Primary Outcome Measures

Objective response rate (ORR)

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)

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)

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)

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)

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

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)

The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Full Information

NCT ID

NCT04444167

First Posted

June 21, 2020

Last Updated

October 17, 2022

Sponsor

Akeso

Collaborators

Akeso Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04444167

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 7, 2020 (Actual)

Primary Completion Date

April 30, 2023 (Anticipated)

Study Completion Date

October 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akeso

Collaborators

Akeso Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Anti-CTLA-4

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AK104 and Lenvatinib

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

AK104

Intervention Description

Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months

Intervention Type

Drug

Intervention Name(s)

Lenvatinib

Intervention Description

Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

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

Time Frame

Up to 2 years

Secondary Outcome Measure Information:

Title

Disease control rate (DCR)

Description

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.

Time Frame

Up to 2 years

Title

Duration of response (DoR)

Description

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

Time Frame

Up to 2 years

Title

Progression-free survival (PFS)

Description

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.

Time Frame

Up to 2 years

Title

Number of participants with adverse events (AEs)

Description

Time Frame

the time of informed consent signed through 90 days after the last dose of AK104 and

Title

Observed concentrations of AK104

Description

The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.

Time Frame

From first dose of AK104 through 90 days after last dose of AK104

Title

Number of subjects who develop detectable anti-drug antibodies (ADAs)

Description

The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Time Frame

From first dose of AK104 through 90 days after last dose of AK104

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Weifeng Song, MD

Phone

+86 (0760) 8987 3999

clinicaltrials@akesobio.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li Bai, MD

Organizational Affiliation

Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Shunchang Jiao, MD

Organizational Affiliation

Chinese PLA General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fangfang Jing, MD

First Name & Middle Initial & Last Name & Degree

Li Bai, MD

First Name & Middle Initial & Last Name & Degree

Shunchang Jiao, MD

12. IPD Sharing Statement

Learn more about this trial

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

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