Sintilimab Plus Bevacizumab as Adjuvant Therapy in HCC Patients at High Risk of Recurrence After Curative Resection

Study Overview
=================
Brief Summary
-----------------
This is an open label, multi-center, randomized, controlled phase III study, to evaluate the efficacy and safety of sintilimab plus bevacizumab as adjuvant therapy in hepatocellular carcinoma (HCC) patients who are at high risk of recurrence after radical resection

Detailed Description
-----------------
There is no stardard adjuvant treatment for HCC. This study is to to evaluate the efficacy and safety of sintilimab plus bevacizumab as adjuvant therapy in HCC patients who are at high risk of recurrence after radical resection.

Official Title
-----------------
A Phase III, Randomized, Open-lable, Multi Center Study of Sintilimab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Curative Hepatic Resection

Conditions
-----------------
HCC, Adjuvant Therapy, Immunotherapy

Intervention / Treatment
-----------------
* Drug: Sintilimab
* Drug: Bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a first diagnosis of HCC who have undergone a curative resection Radiologic evidence of disease free ≥4 weeks after complete surgical resection Full recovery from surgical resection or post-operative transarterial chemoembolization before randomization Randomization needs to occur within 12 weeks of the date of surgical resection High risk for HCC recurrence as protocol defined Child-Pugh Score, Class A ECOG performance status 0 or 1 No prior systemic anticancer therapy for HCC Adequate hematologic and organ function Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC Evidence of residual, recurrent, or metastatic disease at randomization History of hepatic encephalopathy or organ transplantation Patients who are in the waiting list for liver transplantation Patients with Vp4 portal vein thrombosis Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or other immunotherapy Pregnant or lactating women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>sintilimab 200mg + bevacizumab 7.5mg/kg IV Q3W | Drug: Sintilimab<br>* Sintilimab 200mg IV Q3W<br>* Other names: Tyvyt;Drug: Bevacizumab<br>* Bevacizumab 7.5mg/kg IV Q3W<br>* Other names: Byvasda;|
| No Intervention: Arm B<br>Active surveillance | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival (RFS) | RFS is defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC as determined by the investigator, or death due to any cause (whichever occurs first). | up to 36 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS） | OS is defined as the time from the date of randomisation until death due to any cause | up to 48 months after randomization | 
| RFS Rate at 12 and 24 months | RFS rate defined as the proportion of patients without recurrence or death from any cause at 12 and 24 months after randomization. | at 12 and 24 months after randomization | 
| OS Rate at 24 and 36 Months | OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization. | at 24 and 36 months after randomization | 
| TTR(time to recurrence) | TTR is defined as the time the date of randomisation until first documented disease recurrence. | up to 36 months after randomization | 
| Adverse Events (AEs) | The grade of AEs and the number of patients with AEs are assessed by the investigator based on CTCAE v5.0 from the date of randomization to 90 days after last dose of study treatment. | up to 48 months after randomization |