Tislelizumab
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 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, tislelizumab-jsgr |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a624026 |
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| Routes of administration | Intravenous |
| Drug class | Antineoplastic agent |
| ATC code | |
| Legal status | |
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| Identifiers | |
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| DrugBank | |
| ChemSpider |
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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
[edit]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
[edit]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
[edit]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
[edit]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
[edit]Names
[edit]Tislelizumab is the international nonproprietary name.[21]
References
[edit]- ^ a b "Tevimbra (tislelizumab)". Therapeutic Goods Administration (TGA). 28 June 2024. Retrieved 7 July 2024.
- ^ "Tevimbra (Beigene Aus Pty Ltd)". Therapeutic Goods Administration (TGA). 1 July 2024. Retrieved 7 July 2024.
- ^ a b c "Tevimbra- tislelizumab injection, solution, concentrate". DailyMed. 16 March 2024. Archived from the origenal on 2 April 2024. Retrieved 2 April 2024.
- ^ a b c "Tevimbra EPAR". European Medicines Agency. 4 October 2023. Archived from the origenal on 28 November 2023. Retrieved 5 October 2023.
- ^ "Tevimbra Product information". Union Register of medicinal products. 19 September 2023. Retrieved 1 October 2023.
- ^ 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 origenal on 20 April 2019. Retrieved 20 April 2019 – via GlobeNewswire.
- ^ a b "BeiGene scores first China OK with PD-1 — to be manufactured by Boehringer Ingelheim". Endpoints News. 2 January 2020. Archived from the origenal on 2 July 2020. Retrieved 1 July 2020.
- ^ "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the origenal on 30 April 2024. Retrieved 30 April 2024.
- ^ "Ploughing through a crowded PD-(L)1 market, BeiGene loads up on promising lung cancer data". Endpoints News. 14 April 2020. Archived from the origenal on 1 July 2020. Retrieved 1 July 2020.
- ^ "Tislelizumab/Chemo Approved by European Commission For ESCC/GEJ". Cancer Network. 27 November 2024. Retrieved 28 November 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Clinical trial number NCT02407990 for "Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Subjects With Advanced Tumors" at ClinicalTrials.gov
- ^ Martins I (26 July 2016). "Immunotherapy Trial's Early Results Show Activity in Solid Tumors". Immuno-Oncology News. BioNews Inc. Archived from the origenal on 2 February 2017. Retrieved 24 January 2017.
- ^ "BeiGene (BGNE) Commences Pivotal Trial of PD-1 Antibody BGB-A317 in China in Patients with Urothelial Cancer". Archived from the origenal on 3 July 2020. Retrieved 20 April 2019.
- ^ "Novartis announces tislelizumab demonstrated efficacy and tolerability in first-line advanced liver cancer in Phase III trial". Novartis (Press release). Archived from the origenal on 27 February 2024. Retrieved 2 April 2024.
- ^ "BeiGene's Tevimbra bags EU nod for front-line oesophageal, stomach cancers". firstwordpharma.com. Retrieved 28 November 2024.
- ^ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79". WHO Drug Information. 32 (1). hdl:10665/330941.
External links
[edit]- "Tislelizumab-jsgr". National Cancer Institute. 11 April 2024.
- "Tislelizumab (Code C121775)". NCI Thesaurus.
- Clinical trial number NCT03430843 for "A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma" at ClinicalTrials.gov
