Clinical trial NCT03794440: 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）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-07
Enrollment: 595
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: up to 24 months after randomization
measure: Progression-free survival (PFS)
timeFrame: up to 24 months after randomization
Secondary outcomes:
measure: PFS
timeFrame: up to 24 months after randomization
measure: Objective response rate (ORR)
timeFrame: up to 24 months after randomization
measure: Disease control rate (DCR)
timeFrame: up to 24 months after randomization
measure: Duration of response (DOR)
timeFrame: up to 24 months after randomization
measure: Time to progression (TTP)
timeFrame: One assessment was performed every 6 weeks (±7 days) from the time of randomization, and once every 12 weeks (±7 days) after 48 weeks.
measure: Time to response (TTR)
timeFrame: up to 24 months after randomization
measure: PFS
timeFrame: up to 24 months after randomization
measure: Objective response rate (ORR)
timeFrame: up to 24 months after randomization
measure: Time to progression (TTP)
timeFrame: up to 24 months after randomization
measure: Duration of response (DOR)
timeFrame: up to 24 months after randomization
measure: Disease control rate (DCR)
timeFrame: up to 24 months after randomization
measure: Time to response (TTR)
timeFrame: up to 24 months after randomization
measure: Anti-drug antibody (ADA)
timeFrame: up to 24 months after randomization
measure: EORTC QLQ-C30
timeFrame: up to 24 months after randomization
measure: EORTC QLQ-HCC18
timeFrame: up to 24 months after randomization
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Hospital of Fudan University
state: Shanghai
Study officials:
References:
citation: 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.