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Tislelizumab

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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 namesBGB-A317, tislelizumab-jsgr
AHFS/Drugs.comMonograph
MedlinePlusa624026
License data
Pregnancy
category
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 programmed death receptor-1.[3] It is being developed by BeiGene.[6]

Tislelizumab was approved for medical use in China in December 2019,[7] in the European Union in September 2023,[4] and in the United States in March 2024.[8]

Medical uses

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In China, tislelizumab is indicated to treat people with classical Hodgkin lymphoma who have received at least two prior therapies;[7] and to treat people with locally advanced or metastatic urothelial carcinoma with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within twelve months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.[9]

In the EU, tislelizumab is indicated for the treatment of adults with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma after prior platinum-based chemotherapy.[4] In November 2024, the European Commission expanded the indication of tislelizumab for use alongside platinum- and fluoropyrimidine-based chemotherapy to treat patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, and in combination with platinum-based chemotherapy for those with unresectable, locally advanced or metastatic oesophageal squamous cell carcinoma.[10]

In the US, tislelizumab is indicated for the treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.[3]

Adverse effects

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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

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Phase I clinical trial from 2016 has results suggesting an elimination half-life of 11 to 17 days.[14] A 2021 structural and functional analysis suggests a t1/2 of 238 ± 32 minutes, 30- to 80-times higher than pembrolizumab and nivolumab.[15]

History

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Phase I trials began in the US and Australia in June 2015.[16] Some early results were announced in July 2016.[17][14]

A phase II clinical trial for urothelial cancer started in China in 2017.[18]

Tislelizumab "demonstrated efficacy and tolerability" in a multicenter phase III trial for advanced hepatocellular carcinoma started in January 2018.[6][19]

In November 2024, the European Commission expanded the indication of tislelizumab as part of a first-line combination treatment for adults with advanced gastric or oesophageal cancer.[20]

Society and culture

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Names

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Tislelizumab is the international nonproprietary name.[21]

References

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  1. ^ a b "Tevimbra (tislelizumab)". Therapeutic Goods Administration (TGA). 28 June 2024. Retrieved 7 July 2024.
  2. ^ "Tevimbra (Beigene Aus Pty Ltd)". Therapeutic Goods Administration (TGA). 1 July 2024. Retrieved 7 July 2024.
  3. ^ a b c "Tevimbra- tislelizumab injection, solution, concentrate". DailyMed. 16 March 2024. Archived from the original on 2 April 2024. Retrieved 2 April 2024.
  4. ^ a b c "Tevimbra EPAR". European Medicines Agency. 4 October 2023. Archived from the original on 28 November 2023. Retrieved 5 October 2023.
  5. ^ "Tevimbra Product information". Union Register of medicinal products. 19 September 2023. Retrieved 1 October 2023.
  6. ^ a b "BeiGene Initiates Global Phase 3 Trial of Anti-PD-1 Antibody Tislelizumab in Patients with Hepatocellular Carcinoma". BeiGene (Press release). 2 January 2018. Archived from the original on 20 April 2019. Retrieved 20 April 2019 – via GlobeNewswire.
  7. ^ a b "BeiGene scores first China OK with PD-1 — to be manufactured by Boehringer Ingelheim". Endpoints News. 2 January 2020. Archived from the original on 2 July 2020. Retrieved 1 July 2020.
  8. ^ "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
  9. ^ "Ploughing through a crowded PD-(L)1 market, BeiGene loads up on promising lung cancer data". Endpoints News. 14 April 2020. Archived from the original on 1 July 2020. Retrieved 1 July 2020.
  10. ^ "Tislelizumab/Chemo Approved by European Commission For ESCC/GEJ". Cancer Network. 27 November 2024. Retrieved 28 November 2024.
  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. 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. ^ a b Desai J, Markman B, Sandhu SK, Gan HK, Friedlander M, Tran B, et al. (20 May 2016). "A phase I dose-escalation study of BGB-A317, an anti-programmed death-1 (PD-1) mAb in patients with advanced solid tumors". Journal of Clinical Oncology. 34 (15_suppl): 3066. doi:10.1200/JCO.2016.34.15_suppl.3066.
  15. ^ 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.
  16. ^ Clinical trial number NCT02407990 for "Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Subjects With Advanced Tumors" at ClinicalTrials.gov
  17. ^ Martins I (26 July 2016). "Immunotherapy Trial's Early Results Show Activity in Solid Tumors". Immuno-Oncology News. BioNews Inc. Archived from the original on 2 February 2017. Retrieved 24 January 2017.
  18. ^ "BeiGene (BGNE) Commences Pivotal Trial of PD-1 Antibody BGB-A317 in China in Patients with Urothelial Cancer". Archived from the original on 3 July 2020. Retrieved 20 April 2019.
  19. ^ "Novartis announces tislelizumab demonstrated efficacy and tolerability in first-line advanced liver cancer in Phase III trial". Novartis (Press release). Archived from the original on 27 February 2024. Retrieved 2 April 2024.
  20. ^ "BeiGene's Tevimbra bags EU nod for front-line oesophageal, stomach cancers". firstwordpharma.com. Retrieved 28 November 2024.
  21. ^ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79". WHO Drug Information. 32 (1). hdl:10665/330941.
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