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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: AK104
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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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.

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: AK104 and Lenvatinib<br>AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD | Biological: AK104<br>* Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months<br>Drug: Lenvatinib<br>* Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months<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 defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 2 years | 
| 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 | Up to 2 years | 
| 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. | Up to 2 years | 
| 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. | the time of informed consent signed through 90 days after the last dose of AK104 and | 
| Observed concentrations of AK104 | The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration. | From first dose of AK104 through 90 days after last dose of AK104 | 
| 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). | From first dose of AK104 through 90 days after last dose of AK104 | 

 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), Anti-CTLA-4