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Advanced Hepatocellular Carcinoma (HCC)Phase 3NCT04723004

Evaluate the Safety and Efficacy of Toripalimab Combined With Bevacizumab Versus Sorafenib Therapy for HCC

A Phase 3 study testing Toripalimab combined with Bevacizumab and Sorafenib in people with Advanced Hepatocellular Carcinoma (HCC), run by Shanghai Junshi Bioscience Co., Ltd. at 56 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Hepatocellular Carcinoma (HCC)
What is being tested?
Toripalimab combined with Bevacizumab and Sorafenib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
326 participants
Where
56 sitesin 2 countries
Study dates
15 Oct 2020to 31 May 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • History of clear interstitial lung disease or non-infectious pneumonia, unless induced by local radiotherapy; Presence of active tuberculosis during screening period or previous anti-tuberculosis treatment within one year prior to randomization.
  • Any serious acute and chronic infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, not including viral hepatitis.
  • Known history of human immunodeficiency virus (HIV) infection.
  • Previously receiving allogeneic stem cell or solid organ transplantation.
  • Inability to swallow tablets, malabsorption syndrome or any condition that affects gastrointestinal absorption.
  • Known history of serious allergy to any monoclonal antibody, targeted anti- angiogenic drug.
  • Other unsuitable subjects as per the investigators.

Trial locations and contacts

56 sites in 2 countries.

56 sites in 2 countries

China54 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100000

  • China PLA General Hospital

    Beijing, Beijing Municipality, 100000

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100000

  • The First Affiliated Hospital of Bengbu Medical college

    Bengbu, Anhui, 233000

  • Jilin Cancer Hospital

    Changchun, Jilin, 130000

  • Jilin Guowen Hospital

    Changchun, Jilin, 130000

  • Hunan Cancer Hospital

    Changsha, Hunan, 410000

  • Xiangya Hospital of Central South University

    Changsha, Hunan, 410000

  • Sichuan Cancer Hospital

    Chengdu, Sichuan, 610000

  • West China Hospital，Sichuan University

    Chengdu, Sichuan, 610000

  • Army Medical Center of PLA

    Chongqing, Chongqing Municipality, 400000

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 400000

  • The Southwest Hospital Of AMU

    Chongqing, Chongqing Municipality, 400000

  • The First Peoples Hospital of Foshan

    Foshan, Guangdong, 528000

  • The First Affiliated Hospital of Gannan Medical University

    Ganzhou, Jiangxi, 341000

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Gaoxiong, Taiwan, 000800

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510000

  • SSun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510000

  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510000

  • The First Affiliated Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510000

  • Hainan General Hospital

    Haikou, Hainan, 570100

  • ShuLan（HangZhou) Hospital

    Hangzhou, Zhejiang, 310000

  • The First Affiliated Hospital,Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310000

  • ZheJiang Cancer Hospital

    Hangzhou, Zhejiang, 310000

  • ZheJiang Provincial People's Hospital

    Hangzhou, Zhejiang, 310000

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Anhui Cancer Hospital

    Hefei, Anhui, 230000

  • Anhui Provincial Hospital

    Hefei, Anhui, 230000

  • The Second Hospital of Anhui Medical University

    Hefei, Anhui, 230000

  • Shandong Cancer Hospital

    Jinan, Shandong, 250000

  • Yunnan Cancer Hospital

    Kunming, Yunnan, 650000

  • The Frist Hospital of Lanzhou University

    Lanzhou, Gansu, 730000

  • The first Affiliated hospital of Nanchang University

    Nanchang, Jiangxi, 330000

  • The Second Affiliated hospital of Nanchang University

    Nanchang, Jiangxi, 330000

  • NanJing Drum Tower Hospital

    Nanjing, Jiangsu, 210000

  • Nantong Tumor Hospital

    Nantong, Jiangsu, 226000

  • The Affiliated Hospital of Qingdao University

    Qingdao, Shandong, 266000

  • Jia Fan

    Shanghai, 130061

  • Yuebei People's Hospital

    Shaoguan, Guangdong, 512000

  • Liaoning cancer hospital

    Shenyang, Liaoning, 110000

  • MacKay Memorial Hospital

    Taibei, Taiwan, 100

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin, Tianjin Municipality, 300000

  • The First Affiliated Hospital of Wenzhou Medical University

    Wenzhou, Zhejiang, 325000

  • Hubei Cancer Hospital

    Wuhan, Hubei, 430000

  • Tongji Hospital Tongji Medical College Of HUST

    Wuhan, Zhejiang, 430000

  • Xiehe Hospital Tongji Medical College Of HUST

    Wuhan, Zhejiang, 430000

  • Zhongnan Hospital of Wuhan University

    Wuhan, Zhejiang, 430000

  • Gansu Wuwei Tumor Hospital

    Wuwei, Gansu, 733000

  • First Affiliated Hospital of Xian Jiaotong University

    Xi’an, Shanxi, 710000

  • Xi'an International Medical Center Hospital

    Xi’an, Shanxi, 710000

  • The Affiliated Hospital of Xuzhou Medical University

    Xuzhou, Jiangsu, 221000

  • Changhua Christian Hospital

    Zhanghua, Taiwan, 000500

  • he First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450000

  • Henan Provincial Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

Singapore2 sites

  • Curie Oncology

    Singapore, Singapore, 999002

  • Tan Tock Seng Hospital

    Singapore, Singapore, 999002

Other trials in Singapore

About this study

Official title: 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

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.

Being tested
Toripalimab combined with Bevacizumab, Sorafenib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Toripalimab combined with BevacizumabCombination product

    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.

  • SorafenibDrug

    Control group:

    Sorafenib 400mg, po, Bid, continuous administration, until occurrence of termination event specified in the protocol.

Study groups in NCT04723004
Study groupRoleWhat they receive
Experimental groupActive comparatorToripalimab combined with Bevacizumab
Receives: Combination Product: Toripalimab combined with Bevacizumab
Control groupActive comparatorSorafenib
Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 years

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (7)

  1. ORR

    The rate of participants that achieve either a complete response (CR) or a partial response (PR).

    Measured: Up to 2 years

  2. DoR

    Duration from the first time reported partial response or complete response to the first time of disease progression or death.

    Measured: Up to 2 years

  3. Disease Control Rate (DCR)

    Proportion of patients with reduction and non-change in tumor burden of a predefined amount, including complete remission, partial remission and stable disease

    Measured: Up to 2 years

  4. TTP

    Define as the time from randomization to the first documented disease progression

    Measured: Up to 2 years

  5. Incidence of AEs/SAEs as Assessed by CTCAE v5.0

    Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0

    Measured: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years.

  6. TMB

    Correlation between tumor mutation burden (TMB) and the efficacy of Toripalimab combined with Bevacizumab

    Measured: Up to 12 years

  7. ADA

    Serum levels and incidence of Anti-drug antibody of Toripalimab combined with Bevacizumab treatment group

    Measured: Up to 12 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2021
  2. Study start15 Oct 2020
  3. Primary completion31 May 2024
  4. Study completion31 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
326 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04723004
Sponsor's protocol ID
JS001-035-III-HCC
Status last verified
Jul 2026
First submitted
21 Jan 2021
Last updated
13 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 40409323

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Toripalimab combined with Bevacizumab and Sorafenib in people with Advanced Hepatocellular Carcinoma (HCC), run by Shanghai Junshi Bioscience Co., Ltd. at 56 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in China, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04723004, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.

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