Tislelizumab

Tislelizumab
Fab fragment of tislelizumab (green) binding the extracellular domain of PD-1 (pale pink). From PDB entry 7BXA
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetPD-1
Clinical data
Trade namesTevimbra
Other names
Routes of
administration		Intravenous
Drug classAntineoplastic 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]

Medical uses

China

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

  • in December 2019, to treat people with classical Hodgkin’s lymphoma (cHL) who have received at least two prior therapies,[9]
  • and in April 2020, to treat people with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.[10]

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]

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.
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