Tislelizumab

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Tislelizumab
Tislelizumab PB-1 7BXA.png
Fab fragment of tislelizumab (green) binding the extracellular domain of PD-1 (pale pink). From PDB entry 7BXA
Monoclonal antibody
Type Whole antibody
Source Humanized
Target PD-1
Clinical data
Trade names Tevimbra
Other names
  • BGB-A317 [1]
  • Tisle [2]
  • tislelizumab-jsgr [3]
Routes of
administration
Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG

Tislelizumab, sold under the brand name Tevimbra among others, is a humanized monoclonal antibody directed against PD-1. [6] It prevents PD-1 from binding to the ligands PD-L1 and PD-L2 (hence it is a checkpoint inhibitor). It is designed to bind less to Fc gamma receptors. [7] It is being developed by BeiGene (after a period with Celgene Corp). [8]

Contents

Medical uses

China

Tislelizumab was approved by China's National Medical Products Administration:

Adverse effects

Adverse effects include anemia, leukopenia, thrombocytopenia, nausea, increased aspartate transaminase (AST), neutropenia, fatigue, decreased appetite, vomiting, musculoskeletal pain, constipation, hypoproteinemia and rash. [11] Fatal events such as respiratory infection or failure, and hepatic injury have been reported. [12]

Adverse events are more common when combined with chemotherapy. [13]

Pharmacokinetics

Phase I clinical trial from 2016 has results suggesting an elimination half-life of 11 to 17 days. [6] A 2021 structural and functional analysis suggests a t1/2 of 238 ± 32 minutes, 30- to 80-times higher than pembrolizumab and nivolumab. [14]

History

Phase I trials began in the US and Australia in June 2015. [15] Some early results were announced in July 2016. [16] [6]

A phase II clinical trial for urothelial cancer started in China in 2017. [7]

It has completed phase III trial for NSCLC. [17] As of April 2024, no results have been posted.

Tislelizumab "demonstrated efficacy and tolerability" in a multicenter phase III trial for advanced hepatocellular carcinoma started in January 2018. [8] [18]

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References

  1. Lopes JM (27 July 2018). "BeiGene's Therapy Candidate Appears to Eliminate Tumors in Half of Hodgkin's Patients in Phase 2 Trial". Lymphoma News Today. Philadelphia, Pennsylvania, United States: BioNews Services.
  2. Erickson S (3 July 2018). "3 Reasons BeiGene Needs to Be on Your Radar". The Motley Fool. Retrieved 2 November 2019.
  3. 1 2 "Tevimbra- tislelizumab injection, solution, concentrate". DailyMed. 16 March 2024. Retrieved 2 April 2024.
  4. "Tevimbra Product information". Union Register of medicinal products. 19 September 2023. Retrieved 1 October 2023.
  5. "Tevimbra EPAR". European Medicines Agency. 4 October 2023. Retrieved 5 October 2023.
  6. 1 2 3 "Meeting Library - Meeting Library". meetinglibrary.asco.org.
  7. 1 2 "BeiGene (BGNE) Commences Pivotal Trial of PD-1 Antibody BGB-A317 in China in Patients with Urothelial Cancer".
  8. 1 2 LTD B (2 January 2018). "BeiGene Initiates Global Phase 3 Trial of Anti-PD-1 Antibody Tislelizumab in Patients with Hepatocellular Carcinoma". GlobeNewswire News Room (Press release).
  9. "BeiGene scores first China OK with PD-1 — to be manufactured by Boehringer Ingelheim". Endpoints News. 2 January 2020. Retrieved 1 July 2020.
  10. "Ploughing through a crowded PD-(L)1 market, BeiGene loads up on promising lung cancer data". Endpoints News. 14 April 2020. Retrieved 1 July 2020.
  11. Zhou Q, Qin Z, Yan P, Wang Q, Qu J, Chen Y (2023). "Immune-related adverse events with severe pain and ureteral expansion as the main manifestations: a case report of tislelizumab-induced ureteritis/cystitis and review of the literature". Frontiers in Immunology. 14: 1226993. doi: 10.3389/fimmu.2023.1226993 . PMC   10587548 . PMID   37869004.
  12. Zhang L, Geng Z, Hao B, Geng Q (January 2022). "Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody". Cancer Control : Journal of the Moffitt Cancer Center. 29: 10732748221111296. doi:10.1177/10732748221111296. PMC   9358212 . PMID   35926155.
  13. Guo Y, Jia J, Hao Z, Yang J (2023). "Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials". Frontiers in Pharmacology. 14: 1172969. doi: 10.3389/fphar.2023.1172969 . PMC   10318343 . PMID   37408759.
  14. Hong Y, Feng Y, Sun H, Zhang B, Wu H, Zhu Q, et al. (March 2021). "Tislelizumab uniquely binds to the CC' loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage". FEBS Open Bio. 11 (3): 782–792. doi:10.1002/2211-5463.13102. PMC   7931243 . PMID   33527708.
  15. Clinical trial number NCT02407990 for "Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Subjects With Advanced Tumors" at ClinicalTrials.gov
  16. "Immunotherapy Trial's Early Results Show Activity in Solid Tumors". 26 July 2016.
  17. Clinical trial number NCT03358875 for "Comparison of Efficacy and Safety of Anti-PD-1 Antibody BGB-A317 Versus Docetaxel as Treatment in the Second- or Third-line Setting in Patients With NSCLC" at ClinicalTrials.gov
  18. "Novartis announces tislelizumab demonstrated efficacy and tolerability in first-line advanced liver cancer in Phase III trial". Novartis. Retrieved 2 April 2024.