Adjuvant Tislelizumab Plus Lenvatinib for Patients at High-risk of HCC Recurrence After Curative Resection or Ablation

Hepatocellular Carcinoma Clinical Trial

— PREVENT-2  

Official title:

Adjuvant Tislelizumab With or Without Lenvatinib for Patients at High-risk of Hepatocellular Carcinoma Recurrence After Curative Resection or Ablation: a Multicentric, Prospective Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05910970
• Other study ID #: PREVENT-2
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: February 15, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Guangxi Medical University
• Contact: Jian-Hong Zhong, Ph.D
• Phone: +86 771 5301253
• Email: zhongjianhong[@]gxmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Though hepatic resection and ablation are the curative treatments for patients with hepatocellular carcinoma (HCC), the 5-years recurrence-free survival is lower than 30%. In recent years, several immune checkpoint inhibitors have been approved in advanced or unresectable HCC. No study about the safety and efficacy of adjuvant immune checkpoint inhibitors for patients with HCC after hepatectomy is reported.

Description:

Hepatic resection and ablation are the best treatments for patients with early stage hepatocellular carcinoma (HCC) or selected intermediate or advanced disease. However, the postoperative 5-years recurrent rate is up to 70%, for whom recurrence is a major cause of death. In recent years, several immune checkpoint inhibitors have been approved in advanced HCC by official guidelines. At the same time, four randomizead controlled trials about adjvuant immune checkpoint inhibitors for postoperative HCC are ongoing. A prospective cohort study found adjuvant immune checkpoint inhibitors with or without tyrosine kinase inhibitors may improve recurrence-free survival of patients at high-risk of HCC recurrence after curative resection (DOI: 10.1200/JCO.2023.41.16_suppl.4119. Journal of Clinical Oncology 41, no. 16_suppl. 4119). Therefore, the investigators plan to compare the safety and efficacy of adjuvant Tislelizumab plus lenvatinib to Tislelizumab monotherapy for patients with high-risk factor of HCC recurrence after curative resection and ablation in a multicentric, prospective study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age from 18 to 75 years (inclusive);

• Diagnosis of HCC confirmed by postoperative histopathology;

• Underwent curative resection, as defined based on intra- and postoperative criteria;

• With high-risk factors of recurrence after curative treatment, based on preoperative radiological imaging or pathology reports indicating a tumor at least 5 cm in diameter, micro- or macrovascular invasion (Vp1/Vp2), satellite or multinodular tumors, and/or Grade 3/4 pathology;

• No residual cancer detected by radiological imaging in the liver within 8 weeks after curative resection;

• Child-Pugh 5-7 scores liver function;

• Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria:

• Received neoadjuvant immune checkpoint inhibitors or tyrosine kinase inhibitors before resection or ablation;

• A history of other malignancies;

• History of active autoimmune or immunodeficiency diseases;

• Concurrent cardiac, pulmonary, cerebral, or renal dysfunction;

• Loss to follow-up within six months.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Immune Checkpoint Inhibitor
• Recurrence

Intervention

Drug:
• Adjuvant tislelizumab plus lenvatinib
Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab plus lenvatinib treatment for six months, HCC recurrence, or unacceptable adverse events.
• Adjuvant tislelizumab
Patients at high-risk of hepatocellular carcinoma recurrence after curative resection or ablation will receive adjuvant tislelizumab treatment for six months, HCC recurrence, or unacceptable adverse events.

Locations

Country	Name	City	State
China	Jian-Hong Zhong	Nanning

Sponsors (1)

Lead Sponsor	Collaborator
Guangxi Medical University

Country where clinical trial is conducted

China, 

References & Publications (5)

Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8. — View Citation

Chen K, Wei W, Liu L, Deng ZJ, Li L, Liang XM, Guo PP, Qi LN, Zhang ZM, Gong WF, Huang S, Yuan WP, Ma L, Xiang BD, Li LQ, Zhong JH. Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice. Cancer Immunol Immunother. 2022 May;71(5):1063-1074. doi: 10.1007/s00262-021-03060-w. Epub 2021 Sep 24. — View Citation

Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A, Chow P, Qin S. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020 May;16(15):975-989. doi: 10.2217/fon-2020-0162. Epub 2020 Apr 30. Erratum In: Future Oncol. 2020 Oct;16(29):2371. — View Citation

Li L, Wu PS, Liang XM, Chen K, Zhang GL, Su QB, Huo RR, Xie RW, Huang S, Ma L, Zhong JH. Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study. J Gastroenterol. 2023 Oct;58(10):1043-1054. doi: 10.1007/s00535-023-02018-2. Epub 2023 Jul 14. — View Citation

Zhong JH, Ma L, Li LQ. Postoperative therapy options for hepatocellular carcinoma. Scand J Gastroenterol. 2014 Jun;49(6):649-61. doi: 10.3109/00365521.2014.905626. Epub 2014 Apr 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrene-free survival	Recurrene-free survival will be calculated using the Kaplan-Meier method, and differences between groups are assessed for significance using the log-rank test.	3 years
Secondary	Overall survival	Overall survival will be calculated using the Kaplan-Meier method, and differences between groups are assessed for significance using the log-rank test.	3 years
Secondary	Adverse events	Adverse events are expressed as number and percentage.	1 years