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.

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）

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Drug: IBI305; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 595
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. ECOG performance status between 0 and 1
3. No systematic anti-tumor treatment has been performed.(End of postoperative adjuvant chemotherapy for more than 6 months allowed).
4. Barcelona Clinic Liver Cancer stage C. BCLC stage B, not suitable for radical surgery and/or local treatment.
5. At least 1 lesion with measurable disease at baseline by RECIST V1.1.
6. Child-Pugh: <=7
7. Adequate organ and bone marrow function.

Exclusion Criteria:

1. With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues.
2. Have a history of hepatic encephalopathy or have a history of liver transplantation.
3. With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion.
4. Central nervous system (CNS) metastasis.
5. Uncontrolled high blood pressure, systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg after optimal medical treatment.
6. Local treatment for liver lesions within 4 weeks.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sorafenib	Drug: Sorafenib; 400mg PO BID
Experimental: Sintilimab +IBI305	Drug: Sintilimab; 200mg IV d1， Q3W; Other Names: IBI308; Drug: IBI305; 15mg/kg IV d1， Q3W; Other Names: anti-VEGF monoclonal antibody

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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Publications and helpful links

General Publications

• Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. doi: 10.1016/S1470-2045(21)00252-7. Epub 2021 Jun 15. Erratum In: Lancet Oncol. 2021 Aug;22(8):e347.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: CIBI338B301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No