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

• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04723004
• Collaborator: (none)
• Enrollment: 326
• Locations: 56
• Arms: 2
• Anticipated Duration (Months): 50.5
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• 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: Oct 15, 2020
• Anticipated Primary Completion Date: Aug 31, 2022
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

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 Sorafenib	Drug: Sorafenib; Control group: Sorafenib 400mg, po, Bid, continuous administration, until occurrence of termination event specified in the protocol.

Outcome Measures

Primary Outcome Measures

1. Progression-free survival (PFS) [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) [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 [Up to 2 years]

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

2. DoR [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) [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 [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 [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 [Up to 12 years]

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

7. ADA [Up to 12 years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical college	Bengbu	Anhui	China	233000
2	Anhui Cancer Hospital	Hefei	Anhui	China	230000
3	Anhui Provincial Hospital	Hefei	Anhui	China	230000
4	The Second Hospital of Anhui Medical University	Hefei	Anhui	China	230000
5	Beijing Cancer Hospital	Beijing	Beijing	China	100000
6	China PLA General Hospital	Beijing	Beijing	China	100000
7	Peking Union Medical College Hospital	Beijing	Beijing	China	100000
8	Army Medical Center of PLA	Chongqing	Chongqing	China	400000
9	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400000
10	The Southwest Hospital Of AMU	Chongqing	Chongqing	China	400000
11	The Frist Hospital of Lanzhou University	Lanzhou	Gansu	China	730000
12	Gansu Wuwei Tumor Hospital	Wuwei	Gansu	China	733000
13	The First Peoples Hospital of Foshan	Foshan	Guangdong	China	528000
14	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510000
15	SSun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510000
16	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510000
17	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510000
18	Yuebei People's Hospital	Shaoguan	Guangdong	China	512000
19	Hainan General Hospital	Haikou	Hainan	China	570100
20	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150000
21	he First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450000
22	Henan Provincial Cancer Hospital	Zhengzhou	Henan	China	450000
23	Hubei Cancer Hospital	Wuhan	Hubei	China	430000
24	Hunan Cancer Hospital	Changsha	Hunan	China	410000
25	Xiangya Hospital of Central South University	Changsha	Hunan	China	410000
26	NanJing Drum Tower Hospital	Nanjing	Jiangsu	China	210000
27	Nantong Tumor Hospital	Nantong	Jiangsu	China	226000
28	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu	China	221000
29	The First Affiliated Hospital of Gannan Medical University	Ganzhou	Jiangxi	China	341000
30	The first Affiliated hospital of Nanchang University	Nanchang	Jiangxi	China	330000
31	The Second Affiliated hospital of Nanchang University	Nanchang	Jiangxi	China	330000
32	Jilin Cancer Hospital	Changchun	Jilin	China	130000
33	Jilin Guowen Hospital	Changchun	Jilin	China	130000
34	Liaoning cancer hospital	Shenyang	Liaoning	China	110000
35	Shandong Cancer Hospital	Jinan	Shandong	China	250000
36	The Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266000
37	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shanxi	China	710000
38	Xi'an International Medical Center Hospital	Xi'an	Shanxi	China	710000
39	Sichuan Cancer Hospital	Chengdu	Sichuan	China	610000
40	West China Hospital，Sichuan University	Chengdu	Sichuan	China	610000
41	Kaohsiung Medical University Chung-Ho Memorial Hospital	Gaoxiong	Taiwan	China	000800
42	MacKay Memorial Hospital	Taibei	Taiwan	China	100
43	Changhua Christian Hospital	Zhanghua	Taiwan	China	000500
44	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China	300000
45	Yunnan Cancer Hospital	Kunming	Yunnan	China	650000
46	ShuLan（HangZhou) Hospital	Hangzhou	Zhejiang	China	310000
47	The First Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310000
48	ZheJiang Cancer Hospital	Hangzhou	Zhejiang	China	310000
49	ZheJiang Provincial People's Hospital	Hangzhou	Zhejiang	China	310000
50	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325000
51	Tongji Hospital Tongji Medical College Of HUST	Wuhan	Zhejiang	China	430000
52	Xiehe Hospital Tongji Medical College Of HUST	Wuhan	Zhejiang	China	430000
53	Zhongnan Hospital of Wuhan University	Wuhan	Zhejiang	China	430000
54	Jia Fan	Shanghai		China	130061
55	Curie Oncology	Singapore		Singapore	999002
56	Tan Tock Seng Hospital	Singapore		Singapore	999002

Sponsors and Collaborators

• Shanghai Junshi Bioscience Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shanghai Junshi Bioscience Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04723004
• Other Study ID Numbers: JS001-035-III-HCC
• First Posted: Jan 25, 2021
• Last Update Posted: Jun 23, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Bevacizumab; Sorafenib

Study Results

No Results Posted as of Jun 23, 2022