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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: AK105
* Drug: Anlotinib Hydrochloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK105 and anlotinib<br> | Biological: AK105<br>* Anti-PD-1 antibody; IV infusion, 200 mg Q3W<br>Drug: Anlotinib Hydrochloride<br>* multi-targeted receptor TKI; oral administration; every 3 weeks as one cycle administered as 2 weeks on/1 week off<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF, Anti-PD-1, Tyrosine Kinase Inhibitor (TKI), Angiogenesis-related kinases