Chemistry:Tislelizumab

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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.[1] It is being developed by BeOne Medicines.[2]

Tislelizumab was approved for medical use in China in December 2019,[3][4] in the European Union in September 2023,[5] in the United States in March 2024,[6][7] and in Australia in May 2024.[8]

Medical uses

In China, tislelizumab is indicated to treat people with classical Hodgkin lymphoma who have received at least two prior therapies;[4] 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.[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][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;[1] 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.[1]

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.[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

Phase I trials began in the United States 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.[2][19]

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.[20]

References

  1. ↑ 1.0 1.1 1.2 Cite error: Invalid <ref> tag; no text was provided for refs named Tevimbra FDA label
  2. ↑ 2.0 2.1 "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.
  3. ↑ "Tislelizumab: First Approval". Drugs 80 (6): 617–624. April 2020. doi:10.1007/s40265-020-01286-z. PMID 32185681. 
  4. ↑ 4.0 4.1 "BeiGene scores first China OK with PD-1 — to be manufactured by Boehringer Ingelheim". 2 January 2020. https://endpts.com/beigene-scores-first-china-ok-with-pd-1-to-be-manufactured-by-boehringer-ingelheim/. 
  5. ↑ 5.0 5.1 5.2 5.3 Cite error: Invalid <ref> tag; no text was provided for refs named Tevimbra EPAR
  6. ↑ "Novel Drug Approvals for 2024". 29 April 2024. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024. 
  7. ↑ (PDF) New Drug Therapy Approvals 2024 (Report). January 2025. https://www.fda.gov/media/184967/download. Retrieved 21 January 2025. 
  8. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Tevimbra APMDS
  9. ↑ "Ploughing through a crowded PD-(L)1 market, BeiGene loads up on promising lung cancer data". 14 April 2020. https://endpts.com/ploughing-through-a-crowded-pd-l1-market-beigene-loads-up-on-promising-lung-cancer-data/. 
  10. ↑ "Tislelizumab/Chemo Approved by European Commission For ESCC/GEJ". 27 November 2024. https://www.cancernetwork.com/view/tislelizumab-chemo-approved-by-european-commission-for-escc-gej. 
  11. ↑ "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. 2023. doi:10.3389/fimmu.2023.1226993. PMID 37869004. 
  12. ↑ "Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody". Cancer Control 29. January 2022. doi:10.1177/10732748221111296. PMID 35926155. 
  13. ↑ "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. 2023. doi:10.3389/fphar.2023.1172969. PMID 37408759. 
  14. ↑ 14.0 14.1 "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. 20 May 2016. doi:10.1200/JCO.2016.34.15_suppl.3066. 
  15. ↑ "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. March 2021. doi:10.1002/2211-5463.13102. 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. ↑ "Immunotherapy Trial's Early Results Show Activity in Solid Tumors". Immuno-Oncology News. BioNews Inc.. 26 July 2016. https://immuno-oncologynews.com/2016/07/26/beigene-presents-initial-clinical-data-showing-anti-cancer-activity-in-range-of-solid-tumors/. 
  18. ↑ "BeiGene (BGNE) Commences Pivotal Trial of PD-1 Antibody BGB-A317 in China in Patients with Urothelial Cancer". https://www.streetinsider.com/Corporate+News/BeiGene+(BGNE)+Commences+Pivotal+Trial+of+PD-1+Antibody+BGB-A317+in+China+in+Patients+with+Urothelial+Cancer/13068864.html. 
  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. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79". WHO Drug Information 32 (1). 2018. 

Further reading



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