A Phase II Study of AK104 Plus Lenvatinib and TACE in HCC

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of AK104 plus lenvatinib combined with on-demand TACE in participants with unresectable, non-metastatic hepatocellular carcinoma

Official Title
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An Open Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of AK104 Plus Lenvatinib and TACE in the Treatment of Unresectable, Non-metastatic Hepatocellular Carcinoma

Conditions
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Unresectable, Non-metastatic Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: AK104
* Drug: Lenvatinib
* Procedure: TACE


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. CNLC IIa IIb or IIIa The main portal vein was not completely obstructed, Child-Pugh A or B At least one measurable lesion according to RECIST criteria ECOG PS 0-1 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 For HCC lesions ≥ 10 cm in any dimension, imaging evaluation showed that there were more than 10 lesions The main portal vein and the left and right primary branches were clogged with cancer thrombus History of hepatic encephalopathy or liver transplantation 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. Inadequately controlled 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+Lenvatinib+TACE<br>Participants will receive AK104 IV every 3 weeks (Q3W) and Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD The first Transarterial chemoembolization will be performed at the beginning of study. | Biological: AK104<br>* Subjects will receive AK104 until disease progression or for a maximum of 24 months<br>Drug: Lenvatinib<br>* Subjects will receive lenvatinib until disease progression or for a maximum of 24 months<br>Procedure: TACE<br>* On demand TACE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, which ever occurs first. | Up to 2 years | 

Secondary 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 | 
| 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 | 
| 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 |