Skip to main content
SpringerLink
Log in

Larotrectinib: First Global Approval

  • AdisInsight Report
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Larotrectinib (VITRAKVI®) is an orally administered, small molecule, highly-selective, tropomyosin receptor kinase (TRK) inhibitor that was developed by Loxo Oncology in collaboration with Bayer AG as a treatment for adult and paediatric patients whose cancers harbour neurotrophic receptor tyrosine kinase (NTRK) gene fusions. In November 2018 larotrectinib received its first global approval in the USA for the treatment of adult and paediatric patients with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. A registration application for the use of larotrectinib in paediatric and adult patients with locally advanced or metastatic solid tumours with NTRK gene fusion proteins has been submitted in the EU. This article summarizes the milestones in the development of larotrectinib leading to its first approval for the treatment of adult and paediatric patients with solid tumours that have NTRK gene fusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berger S, Martens UM, Bochum S. Larotrectinib (LOXO-101). Recent Results Cancer Res. 2018;211:141–51.

    Article  Google Scholar 

  2. Vaishnavi A, Le A, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25–34.

    Article  CAS  Google Scholar 

  3. Kummar S, Lassen UN. TRK inhibition: a new tumor-agnostic treatment strategy. Target Oncol. 2018;13(5):545–56.

    Article  Google Scholar 

  4. Loxo Oncology. Vitrakvi® (Larotrectinib): US prescribing information. 2018. https://www.fda.gov/. Accessed 04 Dec 2018.

  5. FDA. FDA approves an oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor [media release]. 2018. https://www.fda.gov/. Accessed 2018.

  6. Loxo Oncology. Loxo oncology announces submission of European Marketing Authorization Application for larotrectinib [media release]. 2018. http://www.loxooncology.com. Accessed 06 Dec 2018.

  7. Loxo Oncology. Loxo Oncology announces EMA Orphan Drug Designation granted to LOXO-101 for treatment of soft tissue sarcoma [media release]. 2016. http://www.loxooncology.com. Accessed 06 Dec 2018.

  8. Agency EM. Larotrectinib: orphan designation EU/3/18/1995. 2018. http://www.ema.europa.eu/. Accessed 06 Dec 2018.

  9. Array BioPharma Inc. Loxo Oncology and Array BioPharma announce license and collaboration agreement [media release]. 2013. http:http://www.arraybiopharma.com. Accessed 03 Dec 2018.

  10. Bayer. Bayer and Loxo Oncology to develop and commercialize two therapies that selectively target genetic drivers of cancer [media release]. 2017. http://www.bayer.com. Accessed 03 Dec 2018.

  11. Doebele RC, Davis LE, Vaishnavi A, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov. 2015;5(10):1049–57.

    Article  CAS  Google Scholar 

  12. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. New Engl J Med. 2018;378(8):731–9.

    Article  CAS  Google Scholar 

  13. Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19(5):705–14.

    Article  CAS  Google Scholar 

  14. DuBois SG, Laetsch TW, Federman N, et al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer. 2018;124(21):4241–7.

    Article  CAS  Google Scholar 

  15. Lassen UN, Albert CM, Kummar S, et al. Larotrectinib efficacy and safety in TRK fusion cancer: an expanded clinical dataset showing consistency in an age and tumor agnostic approach [abstract no. 409O plus oral presentation]. Ann Oncol. 2018;29(Suppl 8):133–48.

    Google Scholar 

  16. Loxo Oncology. Loxo Oncology and illumina to partner on developing next-generation sequencing-based pan-cancer companion diagnostics [media release]. 2018. http://ir.loxooncology.com. Accessed 03 Dec 2018.

Download references

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Lesley J. Scott

Authors
  1. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesley J. Scott.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Lesley Scott is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scott, L.J. Larotrectinib: First Global Approval. Drugs 79, 201–206 (2019). https://doi.org/10.1007/s40265-018-1044-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-1044-x

Search

Navigation