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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: AK105; Drug: Anlotinib Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • 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.
• 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.

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: AK105 and anlotinib	Biological: AK105; Anti-PD-1 antibody; IV infusion, 200 mg Q3W; Drug: Anlotinib Hydrochloride; multi-targeted receptor TKI; oral administration; every 3 weeks as one cycle administered as 2 weeks on/1 week off

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is the proportion of subjects with CR or PR based on RECIST v1.1.	up to approximately 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the time of informed consent through 90 days after last dose of AK105
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.	up to approximately 18 months
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD based on RECIST v1.1.	up to approximately 18 months
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).	up to approximately 18 months
Overall survival (OS)	OS is the time from the date of first dosing to death due to any cause.	up to approximately 24 months
Observed concentrations of AK105	The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.	From first dose of AK105 through 90 days after last dose of AK105
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).	From first dose of AK105 through 90 days after last dose of AK105

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2018
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VEGF; Anti-PD-1; Tyrosine Kinase Inhibitor (TKI); Angiogenesis-related kinases
• 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
• Other Study ID Numbers: AK105-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No