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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04723004
Recruitment Status : Active, not recruiting
First Posted : January 25, 2021
Last Update Posted : June 23, 2022
Information provided by (Responsible Party):
Shanghai Junshi Bioscience Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Advanced Hepatocellular Carcinoma (HCC) Combination Product: Toripalimab combined with Bevacizumab Drug: Sorafenib Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 326 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 15, 2020
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Experimental group
Toripalimab combined with Bevacizumab
Combination Product: Toripalimab combined with Bevacizumab

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.

Active Comparator: Control group
Drug: Sorafenib

Control group:

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

Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    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.

  2. Overall survival (OS) [ Time Frame: Up to 2 years ]
    Duration from the date of initial treatment with Toripalimab Plus Bevacizumab or Sorafenib monotherapy to the date of death due to any cause.

Secondary Outcome Measures :
  1. ORR [ Time Frame: Up to 2 years ]
    The rate of participants that achieve either a complete response (CR) or a partial response (PR).

  2. DoR [ Time Frame: Up to 2 years ]
    Duration from the first time reported partial response or complete response to the first time of disease progression or death.

  3. Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
    Proportion of patients with reduction and non-change in tumor burden of a predefined amount, including complete remission, partial remission and stable disease

  4. TTP [ Time Frame: Up to 2 years ]
    Define as the time from randomization to the first documented disease progression

  5. Incidence of AEs/SAEs as Assessed by CTCAE v5.0 [ Time Frame: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately years. ]
    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

  6. TMB [ Time Frame: Up to 12 years ]
    Correlation between tumor mutation burden (TMB) and the efficacy of Toripalimab combined with Bevacizumab

  7. ADA [ Time Frame: Up to 12 years ]
    Serum levels and incidence of Anti-drug antibody of Toripalimab combined with Bevacizumab treatment group

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age of 18-75 years (inclusive), male or female.
  2. 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.
  3. Unresectable BCLC B/C
  4. 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.
  5. ≥ 1 measurable lesion per RECISTv1.1.
  6. Child-Pugh class A, with no history of hepatic encephalopathy.
  7. ECOG PS 0 or 1.
  8. Predicted life expectancy ≥12 weeks.
  9. adequate main organ functions
  10. 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.
  11. 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.
  12. Being voluntary to participate in the study, sufficiently informed consent and signature of written informed consent form, with good compliance.

Exclusion Criteria:

  1. Known ICC or mixed cell carcinoma, sarcomatoid HCC and hepatic fibrolamellar carcinoma.
  2. History of malignancy other than HCC within 5 years prior to screening.
  3. 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).
  4. Prior other anti-PD-1 antibody therapy or other immunotherapy against PD- 1 / PD-L1.
  5. Uncontrolled pericardial effusion, uncontrolled pleural effusion or clinically obvious moderate/severe pleural effusion at screening.
  6. 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.
  7. Having ≥ grade 3 (NCI-CTC AE v5.0) gastrointestinal or non- gastrointestinal fistula at present.
  8. 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.
  9. Serious cardiovascular and cerebrovascular diseases
  10. Having major bleeding and coagulation disorders or other obvious evidence on hemorrhagic tendency:
  11. Medium to large surgical treatment within 4 weeks prior to randomization (except diagnostic biopsy).
  12. Central nervous system metastases.
  13. Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture.
  14. Vaccination of live vaccine within 30 days prior to randomization.
  15. 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.
  16. 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.
  17. Any serious acute and chronic infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, not including viral hepatitis.
  18. Known history of human immunodeficiency virus (HIV) infection.
  19. Previously receiving allogeneic stem cell or solid organ transplantation.
  20. Inability to swallow tablets, malabsorption syndrome or any condition that affects gastrointestinal absorption.
  21. Known history of serious allergy to any monoclonal antibody, targeted anti- angiogenic drug.
  22. Other unsuitable subjects as per the investigators.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04723004

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Sponsors and Collaborators
Shanghai Junshi Bioscience Co., Ltd.
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Responsible Party: Shanghai Junshi Bioscience Co., Ltd. Identifier: NCT04723004    
Other Study ID Numbers: JS001-035-III-HCC
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action