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.

• ClinicalTrials.gov Identifier: NCT03794440
• Recruitment Status: Unknown
• First Posted: January 7, 2019
• Last Update Posted: January 22, 2021
• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Information provided by (Responsible Party): Innovent Biologics (Suzhou) Co. Ltd.

Tracking Information

• First Submitted Date: January 3, 2019
• First Posted Date: January 7, 2019
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: February 11, 2019
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2020)

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

Original Primary Outcome Measures (submitted: January 3, 2019)

• Overall survival (OS) [ Time Frame: up to 24 months after randomization ]
• Objective response rate (ORR) [ Time Frame: up to 24 months after randomization ]
  Objective response rate (ORR) in two arms based on RECIST V1.1 by Independent Radiological Review Committee,IRRC .

Current Secondary Outcome Measures (submitted: July 13, 2020)

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

Original Secondary Outcome Measures (submitted: January 3, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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）
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

• Drug: Sintilimab
  200mg IV d1， Q3W
  Other Name: IBI308
• Drug: IBI305
  15mg/kg IV d1， Q3W
  Other Name: anti-VEGF monoclonal antibody
• Drug: Sorafenib
  400mg PO BID

Study Arms

• Experimental: Sintilimab +IBI305
  Interventions:

  • Drug: Sintilimab
  • Drug: IBI305
• Active Comparator: Sorafenib
  Intervention: Drug: Sorafenib

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: January 21, 2021): 595
• Original Estimated Enrollment (submitted: January 3, 2019): 566
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03794440
• Other Study ID Numbers: CIBI338B301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Innovent Biologics (Suzhou) Co. Ltd.
• Verification Date: May 2020