Study of SHR-8068 Combined With Adebrelimab and Bevacizumab in the Treatment of Advanced Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
To evaluate the tolerability and safety of SHR-8068 in combination with Adebrelimab and Bevacizumab in subjects with advanced HCC; To evaluate the efficacy of SHR-8068 in combination with Adebrelimab and Bevacizumab in subjects with advanced HCC.

Official Title
-----------------
An Open-label, Multicenter Phase Ib/II Clinical Study of SHR-8068 Combined With Adebrelimab and Bevacizumab in the Treatment of Advanced Hepatocellular Carcinoma

Conditions
-----------------
Advanced Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Adebrelimab
* Drug: Bevacizumab
* Drug: SHR-8068


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 75 years old, both male and female; Stage 1: pathologically diagnosed, incurable advanced HCC subjects who have failed standard treatment or were unwilling to accept standard treatment; Stage 2: pathologically diagnosed, incurable advanced HCC subjects, who have no prior immunotherapy, no more than 1 line of previous system treatment; At least one measurable lesion based on RECIST v1.1 criteria; Barcelona clinic liver cancer: Stage B or C; ECOG PS score: 0-1 points; Child-Pugh score: ≤ 7; Expected survival period ≥ 3 months; Adequate organ function. Exclusion Criteria: Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma or mixed cholangiocarcinoma / hepatocellular carcinoma; Patients with any active, known or suspected autoimmune disorder; Systemic treatment with corticosteroids or other immunosuppressants within 1 month before the first dose; With known severe allergic reactions to any other monoclonal antibodies; Patients with known CNS metastasis or hepatic encephalopathy; Patients with liver tumor burden greater than 50% of total liver in volume, or patients who have previously undergone liver transplantation; Patients with symptomatic ascites or pleural effusion requiring paracentesis and drainage, or patients who have undergone ascites or pleural effusion drainage within 2 weeks before the first dose; Patients with other malignancies currently or within the past 5 years; Patients with hypertension which cannot be well controlled by antihypertensives; Uncontrolled cardiac diseases or symptoms; Patients with other potential factors that may affect the study results.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: This study is a multicenter, open-label, dose-finding and efficacy-expansion phase Ib/II study. The phase Ib design is for dose finding and dose confirmation, using modified 3+3 design; the phase II design is for efficacy expansion through randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adebrelimab in combination with Bevacizumab<br> | Drug: Adebrelimab<br>* intravenous infusion<br>Drug: Bevacizumab<br>* intravenous infusion<br>|
| Experimental: Adebrelimab in combination with Bevacizumab and SHR-8068 RP2D1<br> | Drug: Adebrelimab<br>* intravenous infusion<br>Drug: Bevacizumab<br>* intravenous infusion<br>Drug: SHR-8068<br>* intravenous infusion<br>|
| Experimental: Adebrelimab in combination with Bevacizumab and SHR-8068 RP2D2<br> | Drug: Adebrelimab<br>* intravenous infusion<br>Drug: Bevacizumab<br>* intravenous infusion<br>Drug: SHR-8068<br>* intravenous infusion<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | The observation period is 21 days after the first dose | 
| Incidence and severity of grade ≥3 drug-related adverse events and serious adverse events of the two-drug or three-drug combination |  | The observation period is from the time when all informed subjects signed the informed consent to the end of the safety follow-up period, up to 2 years | 
| Objective Response Rate | determined using RECIST v1.1 criteria, defined as best overall response (complete or partial response) across all assessment time points | At the time point of every 6 or 9 weeks, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate, determined using RECIST v1.1 criteria |  | At the time point of every 6 or 9 weeks, up to 2 years | 
| Progression-Free-Survival assessed by investigator |  | up to 2 years] |