A Study to Evaluate the Efficacy and Safety of Sintilimab in Combination With IBI305 (Anti-VEGF Monoclonal Antibody) Compared to Sorafenib as the First-Line Treatment for Advanced Hepatocellular Carcinoma.

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the safety, tolerability and effectiveness of Sintilimab in combination with IBI305 in patients with HCC as the first-line treatment compared with Sorafenib. This study is a randomised, Open-label，Multi-center Study. The primary endpoint is overall survival.

Official Title
-----------------
A Randomized, Open-label，Multi-center Study to Evaluate the Efficacy and Safety of the Combination of Sintilimab and IBI305 Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma. （ORIENT-32）

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

Intervention / Treatment
-----------------
* Drug: Sintilimab
* Drug: IBI305
* Drug: Sorafenib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hepatocellular carcinoma confirmed by histology/cytology. Cirrhosis meets the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Diagnosis of Liver Diseases (AASLD). ECOG performance status between 0 and 1 No systematic anti-tumor treatment has been performed.(End of postoperative adjuvant chemotherapy for more than 6 months allowed). Barcelona Clinic Liver Cancer stage C. BCLC stage B, not suitable for radical surgery and/or local treatment. At least 1 lesion with measurable disease at baseline by RECIST V1.1. Child-Pugh: <=7 Adequate organ and bone marrow function. Exclusion Criteria: With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues. Have a history of hepatic encephalopathy or have a history of liver transplantation. With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion. Central nervous system (CNS) metastasis. Uncontrolled high blood pressure, systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg after optimal medical treatment. Local treatment for liver lesions within 4 weeks.

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: Sintilimab +IBI305<br> | Drug: Sintilimab<br>* 200mg IV d1， Q3W<br>* Other names: IBI308;Drug: IBI305<br>* 15mg/kg IV d1， Q3W<br>* Other names: anti-VEGF monoclonal antibody;|
| Active Comparator: Sorafenib<br> | Drug: Sorafenib<br>* 400mg PO BID<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | up to 24 months after randomization | 
| Progression-free survival (PFS) | Progression-free survival (PFS) in two arms based on RECIST V1.1 by Independent Radiological Review Committee, IRRC. | up to 24 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS in two arms based on RECIST V1.1 by investigator. | up to 24 months after randomization | 
| Objective response rate (ORR) | Objective response rate (ORR) in two arms based on RECIST V1.1 by IRRC and investigator . | up to 24 months after randomization | 
| Disease control rate (DCR) | DCR in two arms based on RECIST V1.1 by IRRC and investigator. | up to 24 months after randomization | 
| Duration of response (DOR) | DOR in two arms based on RECIST V1.1 by IRRC and investigator. | up to 24 months after randomization | 
| Time to progression (TTP) | TTP in two arms based on RECIST V1.1 by IRRC and investigator. | One assessment was performed every 6 weeks (±7 days) from the time of randomization, and once every 12 weeks (±7 days) after 48 weeks. | 
| Time to response (TTR) | TTR in two arms based on RECIST V1.1 by IRRC and investigator. | up to 24 months after randomization | 
| PFS | PFS in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Objective response rate (ORR) | Objective response rate (ORR) in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Time to progression (TTP) | TTP in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Duration of response (DOR) | DOR in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Disease control rate (DCR) | DCR in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Time to response (TTR) | TTR in two arms based on mRECIST by IRRC. | up to 24 months after randomization | 
| Anti-drug antibody (ADA) | Immunogenicity measured by anti-drug antibody (ADA) for Sintilimab and IBI305. | up to 24 months after randomization | 
| EORTC QLQ-C30 |  | up to 24 months after randomization | 
| EORTC QLQ-HCC18 |  | up to 24 months after randomization |