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Larotrectinib, First TRK Inhibitor Approved by the FDA for Solid Tumors
By: Hunan Huateng Pharmaceutical Co. Ltd.
On November 26, 2018,FDA approved larotrectinib (Vitrakvi; Loxo Oncology), the first drug approved for the treatment of adults and pediatric patients with solid tumors that have an 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 after treatment. Larotrectinib received accelerated approval based on overall response rate and duration of response data. Further clinical trials are required to confirm the clinical benefit of larotrectinib.
Commenting on this approval, FDA Commissioner Scott Gottlieb, MD, said, "Today's approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body."
MECHANISM OF ACTION
Larotrectinib is an inhibitor of TRK, including TRKA, TRKB, and TRKC. These kinases are encoded by the genes NTRK1, NTRK2, and NTRK3. Using in vitro and in vivo tumor models, larotrectinib demonstrated antitumor activity in cells with constitutive activation of TRK proteins that resulted from gene fusions or the deletion of a protein regulatory domain, and in cells with TRK protein overexpression. Point mutations in the TRKC kinase domain (ie, G623R, G696A, and F617L) result in resistance to larotrectinib.
DOSING AND ADMINISTRATION
The recommended starting dose of larotrectinib in adults and young patients with a body surface area of ≥1 m2 is 100 mg orally twice daily, with or without food, until disease progression or unacceptable toxicity. For pediatric patients whose body surface area is <1 m2, the recommended starting dose of larotrectinib is <100 mg/m2 orally twice daily.
Larotrectinib, a novel oral inhibitor of TRK, is the first therapy approved for the treatment of adults and pediatric patients with solid tumors associated with an identified NTRK gene fusion. It is approved for patients with solid tumors and this biomarker who have progressive metastatic disease that has no satisfactory alternative treatment. Because this tissue-agnostic drug has demonstrated durable responses and safety in this patient population, larotrectinib represents an innovative milestone in precision medicine and in oncology drug development.
Huateng Pharma, a professional manufacturer of pharmaceutical API and intermediates. We supply many kinds of anti-cancer drugs intermediates such as Carfilzomib intermediates, Palbociclib intermediates, Ribociclib intermediates, Elagolix intermediates and so on. We can also provide Larotrectinib intermediates CAS No.1919868-77-
Hunan Huateng Pharmaceutical Co. Ltd.
Add: Lugu Business Plaza E1, Yuelu District, Changsha City, Hunan Province, P.R. China
zip code: 410205
Telephone: +86 731 89916275
Fax: +86 0731-82251112-