Larotrectinib

Larotrectinib, sold under the brand name Vitrakvi, is a medication for the treatment of cancer.[3][4][5] It is an inhibitor of tropomyosin kinase receptors TrkA, TrkB, and TrkC.[6][7][8] It was discovered by Array BioPharma and licensed to Loxo Oncology in 2013.

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
IUPAC name
  • (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
Chemical and physical data
FormulaC21H22F2N6O2
Molar mass428.444 g·mol−1
3D model (JSmol)
SMILES
  • O[C@H]1CCN(C1)C(=O)Nc2cnn3ccc(nc23)N4CCC[C@@H]4c5cc(F)ccc5F
InChI
  • 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 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.[9] Some clinical trial results were announced in 2017.[10] On 26 November 2018, Larotrectinib was approved by the FDA.[11]

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.[12] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[13]

Phase II clinical trials evaluating the drug for efficacy and safety in treating several types of solid tumors are ongoing.[14]

Larotrectinib was approved for medical use in the European Union in September 2019.[15][16] It was approved for medical use in Australia in August 2020.[3]

References
  1. "Vitrakvi Product information". Health Canada. Retrieved 29 May 2022.
  2. "Summary Basis of Decision (SBD) for Vitrakvi". Health Canada. Retrieved 29 May 2022.
  3. "Vitrakvi". Therapeutic Goods Administration (TGA). 16 September 2020. Retrieved 22 September 2020.
  4. "Vitrakvi- larotrectinib capsule Vitrakvi- larotrectinib solution, concentrate". DailyMed. 26 July 2019. Retrieved 22 September 2020.
  5. "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL" (PDF). ama-assn.org. October 26, 2016.
  6. Berger S, Martens UM, Bochum S (2018). "Larotrectinib (LOXO-101)". Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 211: 141–151. doi:10.1007/978-3-319-91442-8_10. ISBN 978-3-319-91441-1. PMID 30069765.
  7. 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.
  8. Scott LJ (February 2019). "Larotrectinib: First Global Approval". Drugs. 79 (2): 201–206. doi:10.1007/s40265-018-1044-x. PMID 30635837. S2CID 57772716.
  9. "Larotrectinib". AdisInsight. Retrieved 31 January 2017.
  10. Novel Agent Shows Antitumor Activity in TRK-Fusion Cancers. June 2017
  11. "FDA approves larotrectinib for solid tumors with NTRK gene fusions". U.S. Food and Drug Administration (FDA). November 26, 2018.
  12. Dun L (27 November 2018). "FDA approves a new cancer drug targeted to genetic mutation, not cancer type". NBC. Retrieved 3 Dec 2018.
  13. New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
  14. Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)
  15. Gallagher J (2019-09-23). "'Revolutionary' new class of cancer drugs approved". Retrieved 2019-09-30.
  16. "Vitrakvi EPAR". European Medicines Agency (EMA). 23 July 2019. Retrieved 22 September 2020.


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