Evaluate the Safety and Efficacy of Toripalimab Combined With Bevacizumab Versus Sorafenib Therapy for HCC
A Randomized, Open-label, Multi-center Phase III Clinical Study to Evaluate the Safety and Efficacy of Toripalimab (JS001) Combined With Bevacizumab Versus Sorafenib as First-line Therapy for Advanced Hepatocellular Carcinoma
1 other identifier
interventional
326
2 countries
56
Brief Summary
This is a prospective, randomized, open-label, parallel-group, active controlled, multi-center phase III registration clinical study to observe, compare and evaluate the efficacy and safety of Toripalimab (hereafter referred to as JS001) combined with Bevacizumab versus Sorafenib as the first-line therapy for advanced HCC This study will enroll the patients with locally advanced or metastatic hepatocellular carcinoma who could not be radically cured and not receive any prior systemic therapy. The study will use PFS and OS as the co-primary endpoints, with approximately 280 patients planned to be enrolled.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2020
Typical duration for phase_3
56 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 15, 2020
CompletedFirst Submitted
Initial submission to the registry
January 21, 2021
CompletedFirst Posted
Study publicly available on registry
January 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedAugust 14, 2023
August 1, 2023
3 years
January 21, 2021
August 9, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS)
A duration from the date of initial treatment with Toripalimab Plus Bevacizumab or Sorafenib to disease progression (defined by RECIST 1.1) or death of any cause, whichever comes first.
Up to 2 years
Overall survival (OS)
Duration from the date of initial treatment with Toripalimab Plus Bevacizumab or Sorafenib monotherapy to the date of death due to any cause.
Up to 2 years
Secondary Outcomes (7)
ORR
Up to 2 years
DoR
Up to 2 years
Disease Control Rate (DCR)
Up to 2 years
TTP
Up to 2 years
Incidence of AEs/SAEs as Assessed by CTCAE v5.0
From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years.
- +2 more secondary outcomes
Study Arms (2)
Experimental group
ACTIVE COMPARATORToripalimab combined with Bevacizumab
Control group
ACTIVE COMPARATORSorafenib
Interventions
Experimental group: Toripalimab, 240mg, IV infusion, every 3 weeks (q3w). combined with Bevacizumab 15mg/kg, IV infusion, every 3 weeks (q3w), Continuous infusion, in a cycle of 3 weeks (21 days), until occurrence of termination event specified in the protocol.
Control group: Sorafenib 400mg, po, Bid, continuous administration, until occurrence of termination event specified in the protocol.
Eligibility Criteria
You may qualify if:
- Age of 18-75 years (inclusive), male or female.
- Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients per the American Association for the Study of Liver Diseases (AASLD) guideline.
- Unresectable BCLC B/C
- No previous systemic therapy for HCC, patients with prior adjuvant therapy alone who relapsed at 6 months or above after the last adjuvant therapy may be enrolled.
- ≥ 1 measurable lesion per RECISTv1.1.
- Child-Pugh class A, with no history of hepatic encephalopathy.
- ECOG PS 0 or 1.
- Predicted life expectancy ≥12 weeks.
- adequate main organ functions
- In case of HBsAg (+) and/or HBcAb (+), HBV DNA is required to be \< 2000 IU/mL. Patients with anti-HCV antibody positive and HCV- RNA\>1000 copies/mL will be excluded; HBV/HCV co-infected patients will be excluded. patients with a prior history of HCV infection who tested negative for HCV-RNA can be considered HCV uninfected.
- Female subjects of childbearing potential must receive serum pregnancy test within 7 days before randomization and the result should be negative, and should be willing to adopt reliable and effective contraceptive methods during the trial and within 60 days after the last dose of study drug. The male patients whose partners are women of childbearing potential must agree to use reliable and effective contraceptive methods during the trial and within 60 days after the last dose of study drug.
- Being voluntary to participate in the study, sufficiently informed consent and signature of written informed consent form, with good compliance.
You may not qualify if:
- Known ICC or mixed cell carcinoma, sarcomatoid HCC and hepatic fibrolamellar carcinoma.
- History of malignancy other than HCC within 5 years prior to screening.
- Hepatic surgery and/or local therapy or investigational treatment with for HCC within 4 weeks prior to randomization, or palliative radiotherapy for bone metastatic lesion within 2 weeks prior to randomization, or Chinese medicine preparation with anti-liver cancer effect within 2 weeks prior to randomization, and non-recovery (not recovered to ≤ NCI-CTCAE v5.0 grade 1) from side effects of any such treatment (except alopecia).
- Prior other anti-PD-1 antibody therapy or other immunotherapy against PD- 1 / PD-L1.
- Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate/severe pleural effusion at screening.
- History of gastrointestinal hemorrhage within 6 months prior to randomization; the patients with portal hypertension need to receive gastroscopy to exclude the patients with "red sign", if they are considered by investigators to have high risk for hemorrhage (including moderate-to-severe esophageal and/or gastric varices with hemorrhagic risk, locally active peptic ulcer and persistent fecal occult blood (+)). The patient needs to be excluded if there is a history of "red sign" in gastroscopy.
- Having ≥ grade 3 (NCI-CTC AE v5.0) gastrointestinal or non- gastrointestinal fistula at present.
- Cancer thrombus in the main trunk of portal vein involving contralateral portal vein branch, or involving superior mesenteric vein. Cancer thrombus in inferior vena cava should be excluded.
- Serious cardiovascular and cerebrovascular diseases
- Having major bleeding and coagulation disorders or other obvious evidence on hemorrhagic tendency:
- Medium to large surgical treatment within 4 weeks prior to randomization (except diagnostic biopsy).
- Central nervous system metastases.
- Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture.
- Vaccination of live vaccine within 30 days prior to randomization.
- Active autoimmune diseases requiring systemic treatment (i.e., immunomodulatory drug, corticosteroid or immunosuppressant) in the past 2 years; however, replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for renal or pituitary insufficiency), inhaled or topical corticosteroids will not be excluded.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (56)
The First Affiliated Hospital of Bengbu Medical college
Bengbu, Anhui, 233000, China
Anhui Cancer Hospital
Hefei, Anhui, 230000, China
Anhui Provincial Hospital
Hefei, Anhui, 230000, China
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230000, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100000, China
China PLA General Hospital
Beijing, Beijing Municipality, 100000, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100000, China
Army Medical Center of PLA
Chongqing, Chongqing Municipality, 400000, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400000, China
The Southwest Hospital Of AMU
Chongqing, Chongqing Municipality, 400000, China
The Frist Hospital of Lanzhou University
Lanzhou, Gansu, 730000, China
Gansu Wuwei Tumor Hospital
Wuwei, Gansu, 733000, China
The First Peoples Hospital of Foshan
Foshan, Guangdong, 528000, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510000, China
SSun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510000, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510000, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510000, China
Yuebei People's Hospital
Shaoguan, Guangdong, 512000, China
Hainan General Hospital
Haikou, Hainan, 570100, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
he First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450000, China
Henan Provincial Cancer Hospital
Zhengzhou, Henan, 450000, China
Hubei Cancer Hospital
Wuhan, Hubei, 430000, China
Hunan Cancer Hospital
Changsha, Hunan, 410000, China
Xiangya Hospital of Central South University
Changsha, Hunan, 410000, China
NanJing Drum Tower Hospital
Nanjing, Jiangsu, 210000, China
Nantong Tumor Hospital
Nantong, Jiangsu, 226000, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221000, China
The First Affiliated Hospital of Gannan Medical University
Ganzhou, Jiangxi, 341000, China
The first Affiliated hospital of Nanchang University
Nanchang, Jiangxi, 330000, China
The Second Affiliated hospital of Nanchang University
Nanchang, Jiangxi, 330000, China
Jilin Cancer Hospital
Changchun, Jilin, 130000, China
Jilin Guowen Hospital
Changchun, Jilin, 130000, China
Liaoning cancer hospital
Shenyang, Liaoning, 110000, China
Shandong Cancer Hospital
Jinan, Shandong, 250000, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266000, China
First Affiliated Hospital of Xian Jiaotong University
Xi’an, Shanxi, 710000, China
Xi'an International Medical Center Hospital
Xi’an, Shanxi, 710000, China
Sichuan Cancer Hospital
Chengdu, Sichuan, 610000, China
West China Hospital，Sichuan University
Chengdu, Sichuan, 610000, China
Kaohsiung Medical University Chung-Ho Memorial Hospital
Gaoxiong, Taiwan, 000800, China
MacKay Memorial Hospital
Taibei, Taiwan, 100, China
Changhua Christian Hospital
Zhanghua, Taiwan, 000500, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, Tianjin Municipality, 300000, China
Yunnan Cancer Hospital
Kunming, Yunnan, 650000, China
ShuLan（HangZhou) Hospital
Hangzhou, Zhejiang, 310000, China
The First Affiliated Hospital,Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000, China
ZheJiang Cancer Hospital
Hangzhou, Zhejiang, 310000, China
ZheJiang Provincial People's Hospital
Hangzhou, Zhejiang, 310000, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Tongji Hospital Tongji Medical College Of HUST
Wuhan, Zhejiang, 430000, China
Xiehe Hospital Tongji Medical College Of HUST
Wuhan, Zhejiang, 430000, China
Zhongnan Hospital of Wuhan University
Wuhan, Zhejiang, 430000, China
Jia Fan
Shanghai, 130061, China
Curie Oncology
Singapore, 999002, Singapore
Tan Tock Seng Hospital
Singapore, 999002, Singapore
Related Publications (1)
Shi Y, Han G, Zhou J, Shi X, Jia W, Cheng Y, Jin Y, Hua X, Wen T, Wu J, Gu S, Bai Y, Wang X, Zhang T, Chen Z, Zhang B, Huang M, Liu H, Mao Y, Zhou L, Wang R, Shan Y, Zhang W, Song T, Guo Y, Zhou F, Shao B, Zhang M, Liang B, Zheng J, Zhang G, Shen J, Su W, Zhang F, He Y, Hu S, Liu R, Zhang C, Shen S, Zeng H, Wang TE, Guo W, Shen Y, Chen Y, Li Y, Samol J, Hu H, Zhang W, Du C, Li E, Liu C, Pin CS, Li X, Xu H, Huang JF, Hao C, Lv J, Wang W, Xu Q, Bai A, Zhang X, Liu B, Jin C, Fan J. Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial. Lancet Gastroenterol Hepatol. 2025 Jul;10(7):658-670. doi: 10.1016/S2468-1253(25)00059-7. Epub 2025 May 20.
PMID: 40409323DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 21, 2021
First Posted
January 25, 2021
Study Start
October 15, 2020
Primary Completion
October 31, 2023
Study Completion
December 31, 2024
Last Updated
August 14, 2023
Record last verified: 2023-08