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 namesBGB-A317, tislelizumab-jsgr
AHFS/Drugs.com Monograph
MedlinePlus a624026
License data
Pregnancy
category
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 an anti-cancer medication used for the treatment of various forms of cancer. It is a humanized monoclonal antibody directed against programmed death receptor-1. [4] It is being developed by BeOne Medicines. [7]

Contents

Tislelizumab was approved for medical use in China in December 2019, [8] [9] in the European Union in September 2023, [5] in the United States in March 2024, [10] [11] and in Australia in May 2024. [1]

Medical uses

In China, tislelizumab is indicated to treat people with classical Hodgkin lymphoma who have received at least two prior therapies; [9] 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. [12]

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. [5] In November 2024, the European Commission expanded the indication of tislelizumab for use alongside platinum- and fluoropyrimidine-based chemotherapy to treat people 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 esophageal squamous cell carcinoma. [5] [13]

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; [4] and, in combination with platinum and fluoropyrimidine-based chemotherapy, it is indicated for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1. [4]

Adverse effects

Adverse effects include anemia, leukopenia, thrombocytopenia, nausea, increased aspartate transaminase (AST), neutropenia, fatigue, decreased appetite, vomiting, musculoskeletal pain, constipation, hypoproteinemia and rash. [14] Fatal events such as respiratory infection or failure, and hepatic injury have been reported. [15]

Adverse events are more common when combined with chemotherapy. [16]

Pharmacokinetics

Phase I clinical trial from 2016 has results suggesting an elimination half-life of 11 to 17 days. [17] A 2021 structural and functional analysis suggests a t1/2 of 238 ± 32 minutes, 30- to 80-times higher than pembrolizumab and nivolumab. [18]

History

Phase I trials began in the United States and Australia in June 2015. [19] Some early results were announced in July 2016. [20] [17]

A phase II clinical trial for urothelial cancer started in China in 2017. [21]

Tislelizumab "demonstrated efficacy and tolerability" in a multicenter phase III trial for advanced hepatocellular carcinoma started in January 2018. [7] [22]

In November 2024, the European Medicines Agency expanded the indication of tislelizumab as part of a first-line combination treatment for adults with advanced gastric or esophageal cancer. [5]

Society and culture

Names

Tislelizumab is the international nonproprietary name. [23]

References

  1. 1 2 3 "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. ↑ "Tevimbra tislelizumab 100 mg/10 mL concentrated injection vial (391176)". Therapeutic Goods Administration (TGA). 31 May 2024. Retrieved 27 December 2024.
  4. 1 2 3 4 "Tevimbra- tislelizumab injection, solution, concentrate". DailyMed. 16 March 2024. Archived from the original on 2 April 2024. Retrieved 2 April 2024.
  5. 1 2 3 4 5 "Tevimbra EPAR". European Medicines Agency (EMA). 4 October 2023. Archived from the original on 28 November 2023. Retrieved 5 October 2023.
  6. ↑ "Tevimbra Product information". Union Register of medicinal products. 19 September 2023. Retrieved 1 October 2023.
  7. 1 2 "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.
  8. ↑ Lee A, Keam SJ (April 2020). "Tislelizumab: First Approval". Drugs. 80 (6): 617–624. doi:10.1007/s40265-020-01286-z. PMID   32185681.
  9. 1 2 "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.
  10. ↑ "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.
  11. ↑ New Drug Therapy Approvals 2024 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2025. Archived from the original on 21 January 2025. Retrieved 21 January 2025.
  12. ↑ "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.
  13. ↑ "Tislelizumab/Chemo Approved by European Commission For ESCC/GEJ". Cancer Network. 27 November 2024. Retrieved 28 November 2024.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. 1 2 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.
  18. ↑ 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.
  19. ↑ Clinical trial number NCT02407990 for "Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Subjects With Advanced Tumors" at ClinicalTrials.gov
  20. ↑ 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.
  21. ↑ "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.
  22. ↑ "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.
  23. ↑ 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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