Larotrectinib

Chemical compound

  • US DailyMed: Larotrectinib
Pregnancy
category
  • AU: D
Routes of
administrationBy mouth, oropharyngealATC code
  • L01EX12 (WHO)
Legal statusLegal status
  • AU: S4 (Prescription only)
  • CA: ℞-only[1][2]
  • UK: POM (Prescription only)[3]
  • US: ℞-only
  • EU: Rx-only
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
  • 1223403-58-4
PubChem CID
  • 46188928
DrugBank
  • DB14723
ChemSpider
  • 44210503
UNII
  • PF9462I9HX
KEGG
  • D11137
  • as salt: D11138
ChEMBL
  • ChEMBL3889654
Chemical and physical dataFormulaC21H22F2N6O2Molar mass428.444 g·mol−13D model (JSmol)
  • Interactive image
  • 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.[4][5][6] It is an inhibitor of tropomyosin kinase receptors TrkA, TrkB, and TrkC.[7][8][9] 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.[10] Some clinical trial results were announced in 2017.[11] On 26 November 2018, Larotrectinib was approved by the FDA.[12]

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.[13] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[14]

Phase II clinical trials evaluating the drug for efficacy and safety in treating several types of solid tumors are ongoing.[15]

Larotrectinib was approved for medical use in the European Union in September 2019.[16][17] It was approved for medical use in Australia in August 2020.[4]

References

  1. ^ "Vitrakvi Product information". Health Canada. 25 April 2012. Retrieved 29 May 2022.
  2. ^ "Summary Basis of Decision (SBD) for Vitrakvi". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ^ "Vitrakvi 25mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 7 March 2022. Retrieved 28 November 2022.
  4. ^ a b "Vitrakvi". Therapeutic Goods Administration (TGA). 16 September 2020. Retrieved 22 September 2020.
  5. ^ "Vitrakvi- larotrectinib capsule Vitrakvi- larotrectinib solution, concentrate". DailyMed. 26 July 2019. Retrieved 22 September 2020.
  6. ^ "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL" (PDF). ama-assn.org. 26 October 2016.
  7. ^ Berger S, Martens UM, Bochum S (2018). "Larotrectinib (LOXO-101)". Small Molecules in Oncology. Recent Results in Cancer Research. Vol. 211. pp. 141–151. doi:10.1007/978-3-319-91442-8_10. ISBN 978-3-319-91441-1. PMID 30069765. {{cite book}}: |journal= ignored (help)
  8. ^ 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.
  9. ^ Scott LJ (February 2019). "Larotrectinib: First Global Approval". Drugs. 79 (2): 201–206. doi:10.1007/s40265-018-1044-x. PMID 30635837. S2CID 57772716.
  10. ^ "Larotrectinib". AdisInsight. Retrieved 31 January 2017.
  11. ^ Novel Agent Shows Antitumor Activity in TRK-Fusion Cancers. June 2017
  12. ^ "FDA approves larotrectinib for solid tumors with NTRK gene fusions". U.S. Food and Drug Administration (FDA). 26 November 2018.
  13. ^ Dun L (27 November 2018). "FDA approves a new cancer drug targeted to genetic mutation, not cancer type". NBC. Retrieved 3 December 2018.
  14. ^ New Drug Therapy Approvals 2018 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2019. Retrieved 16 September 2020.
  15. ^ Bayer (17 February 2023). "A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors" – via ClinicalTrials.gov. {{cite journal}}: Cite journal requires |journal= (help)
  16. ^ Gallagher J (23 September 2019). "'Revolutionary' new class of cancer drugs approved". Retrieved 30 September 2019.
  17. ^ "Vitrakvi EPAR". European Medicines Agency (EMA). 23 July 2019. Retrieved 22 September 2020.

External links

  • "Larotrectinib". Drug Information Portal. U.S. National Library of Medicine.
  • "Larotrectinib sulfate". National Cancer Institute. 6 December 2018.
  • "Larotrectinib sulfate". NCI Dictionary of Cancer Terms. National Cancer Institute.
  • v
  • t
  • e
CI monoclonal antibodies ("-mab")
Receptor tyrosine kinase
Others for solid tumors
Leukemia/lymphoma
Other
Tyrosine kinase inhibitors ("-nib")
Receptor tyrosine kinase
Non-receptor
Other
  • v
  • t
  • e
Angiopoietin
  • Kinase inhibitors: Altiratinib
  • CE-245677
  • Rebastinib
CNTF
EGF (ErbB)
EGF
(ErbB1/HER1)
ErbB2/HER2
  • Agonists: Unknown/none
ErbB3/HER3
ErbB4/HER4
FGF
FGFR1
FGFR2
  • Antibodies: Aprutumab
  • Aprutumab ixadotin
FGFR3
FGFR4
Unsorted
HGF (c-Met)
IGF
IGF-1
  • Kinase inhibitors: BMS-754807
  • Linsitinib
  • NVP-ADW742
  • NVP-AEW541
  • OSl-906
IGF-2
  • Antibodies: Dusigitumab
  • Xentuzumab (against IGF-1 and IGF-2)
Others
  • Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1)
  • Trofinetide
LNGF (p75NTR)
  • Aptamers: Against NGF: RBM-004
  • Decoy receptors: LEVI-04 (p75NTR-Fc)
PDGF
RET (GFL)
GFRα1
GFRα2
GFRα3
GFRα4
Unsorted
  • Kinase inhibitors: Agerafenib
SCF (c-Kit)
TGFβ
  • See here instead.
Trk
TrkA
  • Negative allosteric modulators: VM-902A
  • Kinase inhibitors: Altiratinib
  • AZD-6918
  • CE-245677
  • CH-7057288
  • DS-6051
  • Entrectinib
  • GZ-389988
  • K252a
  • Larotrectinib
  • Lestaurtinib
  • Milciclib
  • ONO-4474
  • ONO-5390556
  • PLX-7486
  • Rebastinib
  • SNA-120 (pegylated K252a))
  • Aptamers: Against NGF: RBM-004
  • Decoy receptors: ReN-1820 (TrkAd5)
TrkB
  • Kinase inhibitors: Altiratinib
  • AZD-6918
  • CE-245677
  • CH-7057288
  • DS-6051
  • Entrectinib
  • GZ-389988
  • K252a
  • Larotrectinib
  • Lestaurtinib
  • ONO-4474
  • ONO-5390556
  • PLX-7486
TrkC
  • Kinase inhibitors: Altiratinib
  • AZD-6918
  • CE-245677
  • CH-7057288
  • DS-6051
  • Entrectinib
  • GZ-389988
  • K252a
  • Larotrectinib
  • Lestaurtinib
  • ONO-4474
  • ONO-5390556
  • PLX-7486
VEGF
Others
Portal:
  • icon Medicine


Stub icon

This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.

  • v
  • t
  • e