Larotrectinib

Larotrectinib
Clinical data
Trade namesVitrakvi
Other namesLOXO-101, ARRY-470
AHFS/Drugs.comMonograph
MedlinePlusa619006
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth, oropharyngeal
ATC code
Legal status
Legal status
Identifiers
  • (3S)-N-{5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxypyrrolidine-1-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H22F2N6O2
Molar mass428.444 g·mol−1
3D model (JSmol)
  • O[C@H]1CCN(C1)C(=O)Nc2cnn3ccc(nc23)N4CCC[C@@H]4c5cc(F)ccc5F
  • InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1
  • Key:NYNZQNWKBKUAII-KBXCAEBGSA-N

Larotrectinib, sold under the brand name Vitrakvi, is a medication for the treatment of cancer.[1][5][7] It is an inhibitor of tropomyosin kinase receptors TrkA, TrkB, and TrkC.[8][9][10] It was discovered by Array BioPharma and licensed to Loxo Oncology in 2013.

Larotrectinib was initially awarded orphan drug status in 2015, for soft tissue sarcoma, and breakthrough therapy designation in 2016 for the treatment of metastatic solid tumors with NTRK fusion.[11] Some clinical trial results were announced in 2017.[12] On 26 November 2018, Larotrectinib was approved by the FDA.[13]

Larotrectinib was the first drug to be specifically developed and approved to treat any cancer containing certain mutations, as opposed to cancers of specific tissues (i.e., the approval is "tissue agnostic"). Several earlier drugs, including pembrolizumab, were eventually approved by the FDA for treatment of specific mutations independent of the type of cancer, but those drugs had been initially developed for specific cancer types.[14] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[15]

Larotrectinib was approved for medical use in the European Union in September 2019.[16][6] It was approved for medical use in Australia in August 2020.[1]

Research

Phase II clinical trials evaluating the drug for efficacy and safety in treating several types of solid tumors are ongoing.[17]

References

  1. ^ a b c "Vitrakvi". Therapeutic Goods Administration (TGA). 16 September 2020. Archived from the original on 19 September 2020. Retrieved 22 September 2020.
  2. ^ "Vitrakvi Product information". Health Canada. 25 April 2012. Archived from the original on 30 May 2022. Retrieved 29 May 2022.
  3. ^ "Summary Basis of Decision (SBD) for Vitrakvi". Health Canada. 23 October 2014. Archived from the original on 31 May 2022. Retrieved 29 May 2022.
  4. ^ "Vitrakvi 25mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 7 March 2022. Archived from the original on 28 November 2022. Retrieved 28 November 2022.
  5. ^ a b "Vitrakvi- larotrectinib capsule Vitrakvi- larotrectinib solution, concentrate". DailyMed. 26 July 2019. Archived from the original on 7 April 2021. Retrieved 22 September 2020.
  6. ^ a b "Vitrakvi EPAR". European Medicines Agency (EMA). 23 July 2019. Archived from the original on 2 October 2020. Retrieved 22 September 2020.
  7. ^ "Larotrectinib" (PDF). Statement on a Nonproprietary Name Adopted by the USAN Council. American Medical Association (AMA). 26 October 2016. Archived (PDF) from the original on 13 March 2018. Retrieved 31 January 2017.
  8. ^ Berger S, Martens UM, Bochum S (2018). "Larotrectinib (LOXO-101)". Small Molecules in Oncology. Recent Results in Cancer Research Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Vol. 211. pp. 141–151. doi:10.1007/978-3-319-91442-8_10. ISBN 978-3-319-91441-1. PMID 30069765.
  9. ^ Federman N, McDermott R (October 2019). "Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer". Expert Review of Clinical Pharmacology. 12 (10): 931–939. doi:10.1080/17512433.2019.1661775. PMID 31469968.
  10. ^ Scott LJ (February 2019). "Larotrectinib: First Global Approval". Drugs. 79 (2): 201–206. doi:10.1007/s40265-018-1044-x. PMID 30635837. S2CID 57772716.
  11. ^ "Larotrectinib". AdisInsight. Archived from the original on 12 March 2018. Retrieved 31 January 2017.
  12. ^ "Novel Agent Shows Antitumor Activity in TRK-Fusion Cancers. June 2017". Archived from the original on 24 January 2021. Retrieved 9 June 2017.
  13. ^ "FDA approves larotrectinib for solid tumors with NTRK gene fusions". U.S. Food and Drug Administration (FDA). 26 November 2018. Archived from the original on 24 March 2021. Retrieved 22 September 2020.
  14. ^ Dun L (27 November 2018). "FDA approves a new cancer drug targeted to genetic mutation, not cancer type". NBC. Archived from the original on 2 December 2018. Retrieved 3 December 2018.
  15. ^ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Archived from the original on 17 September 2020. Retrieved 16 September 2020.
  16. ^ Gallagher J (23 September 2019). "'Revolutionary' new class of cancer drugs approved". Archived from the original on 26 September 2019. Retrieved 30 September 2019.
  17. ^ Clinical trial number NCT02576431 for "A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors" at ClinicalTrials.gov


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