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A Study of the Combination of Anti-PD-1 AK105 and Anlotinib in First-line Hepatocellular Carcinoma (HCC)

Primary Purpose

Hepatocellular Carcinoma

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

AK105

Anlotinib Hydrochloride

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

Signed written informed consent form voluntarily.
Male or female，age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF.
Expected life expectance ≥ 3 months.
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Confirmation either by histology unresectable hepatocellular carcinoma..
BCLC stage C, and non-resectable BCLC stage B .
No prior systemic therapy for HCC.
Child-Pugh class A and B (≤7 points).
At least one measurable lesion according to RECIST criteria.
Adequate hematologic and end-organ function.
For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent.

Exclusion Criteria:

Prior treatment with anti-PD1, anti-PD-L1 or anti-CTLA-4 antibody therapy.
Active ongoing infection requiring therapy.
History of severe hypersensitivity reaction to another monoclonal antibody.
Received any live attenuated vaccine within the last 30 days.
Other malignancy requiring treatment in the prior 5 years with the exception of locally treated squamous or basal cell carcinoma.
Pregnant, breast feeding, or planning to become pregnant.
Active or prior documented autoimmune or inflammatory disease with some exceptions.
Central nervous system metastases and/or carcinomatous meningitis.
Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
Co-infection of HBV and HCV.
Inadequately controlled arterial hypertension.

Sites / Locations

Chinese PLA General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AK105 and anlotinib

Arm Description

Outcomes

Primary Outcome Measures

Objective response rate (ORR)

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

Secondary Outcome Measures

Number of subjects experiencing 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.

Duration of response (DoR)

DoR 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.

Disease control rate (DCR)

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

Progression-free survival (PFS)

PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).

Overall survival (OS)

OS is the time from the date of first dosing to death due to any cause.

Observed concentrations of AK105

The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.

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

The immunogenicity of AK105 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Full Information

NCT ID

NCT04172571

First Posted

November 19, 2019

Last Updated

October 11, 2022

Sponsor

Akeso

Collaborators

Akeso Tiancheng, Inc

1. Study Identification

Unique Protocol Identification Number

NCT04172571

Brief Title

A Study of the Combination of Anti-PD-1 AK105 and Anlotinib in First-line Hepatocellular Carcinoma (HCC)

Official Title

An Open-Label Multi-Center Phase Ib/II Study of the Combination of AK105 and Anlotinib Hydrochloride in the First-Line Treatment of Patients With Unresectable Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 22, 2018 (Actual)

Primary Completion Date

June 1, 2022 (Actual)

Study Completion Date

November 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akeso

Collaborators

Akeso Tiancheng, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multi-center,open-label study to evaluate the efficacy and safety of anti-PD-1 antibody AK105 plus anlotinib hydrochloride in the first-line treatment of patients with unresectable 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), Angiogenesis-related kinases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AK105 and anlotinib

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

AK105

Intervention Description

Anti-PD-1 antibody; IV infusion, 200 mg Q3W

Intervention Type

Drug

Intervention Name(s)

Anlotinib Hydrochloride

Intervention Description

multi-targeted receptor TKI; oral administration; every 3 weeks as one cycle administered as 2 weeks on/1 week off

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

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

Time Frame

up to approximately 18 months

Secondary Outcome Measure Information:

Title

Number of subjects experiencing adverse events (AEs)

Description

Time Frame

From the time of informed consent through 90 days after last dose of AK105

Title

Duration of response (DoR)

Description

DoR 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 approximately 18 months

Title

Disease control rate (DCR)

Description

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

Time Frame

up to approximately 18 months

Title

Progression-free survival (PFS)

Description

Time Frame

up to approximately 18 months

Title

Overall survival (OS)

Description

OS is the time from the date of first dosing to death due to any cause.

Time Frame

up to approximately 24 months

Title

Observed concentrations of AK105

Description

The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.

Time Frame

From first dose of AK105 through 90 days after last dose of AK105

Title

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

Description

The immunogenicity of AK105 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Time Frame

From first dose of AK105 through 90 days after last dose of AK105

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. Male or female，age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the ICF. Expected life expectance ≥ 3 months. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. Confirmation either by histology unresectable hepatocellular carcinoma.. BCLC stage C, and non-resectable BCLC stage B . No prior systemic therapy for HCC. Child-Pugh class A and B (≤7 points). At least one measurable lesion according to RECIST criteria. Adequate hematologic and end-organ function. For women of childbearing potential: agreement to remain abstinent; For men: agreement to remain abstinent. Exclusion Criteria: Prior treatment with anti-PD1, anti-PD-L1 or anti-CTLA-4 antibody therapy. Active ongoing infection requiring therapy. History of severe hypersensitivity reaction to another monoclonal antibody. Received any live attenuated vaccine within the last 30 days. Other malignancy requiring treatment in the prior 5 years with the exception of locally treated squamous or basal cell carcinoma. Pregnant, breast feeding, or planning to become pregnant. Active or prior documented autoimmune or inflammatory disease with some exceptions. Central nervous system metastases and/or carcinomatous meningitis. Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication. Co-infection of HBV and HCV. Inadequately controlled arterial hypertension.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shunchang Jiao, MD

Organizational Affiliation

Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Li Bai, 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

ZIP/Postal Code

100730

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35833116

Citation

Huang Z, Pang X, Zhong T, Qu T, Chen N, Ma S, He X, Xia D, Wang M, Xia M, Li B. Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events. Front Immunol. 2022 Jun 27;13:924542. doi: 10.3389/fimmu.2022.924542. eCollection 2022.

Results Reference

derived

PubMed Identifier

34327136

Citation

Han C, Ye S, Hu C, Shen L, Qin Q, Bai Y, Yang S, Bai C, Zang A, Jiao S, Bai L. Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203). Front Oncol. 2021 Jul 13;11:684867. doi: 10.3389/fonc.2021.684867. eCollection 2021.

Results Reference

derived

Learn more about this trial

A Study of the Combination of Anti-PD-1 AK105 and Anlotinib in First-line Hepatocellular Carcinoma (HCC)

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