On November 26, 2018, the U.S. Food and Drug Administration granted accelerated approval to Vitrakvi (larotrectinib), a treatment for adult and pediatric patients whose cancers have a specific genetic feature (biomarker)1, 2. The approval is for the treatment of adult and pediatric patients3 with solid tumors with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity and have no satisfactory alternative treatments or have progressed following treatment.
This is the second time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated. The approval marks a new paradigm in the development of cancer drugs that are "tissue agnostic."
Larotrectinib demonstrated a 75 percent overall response rate across different types of solid tumors. These responses were durable, with 73 percent of responses lasting at least six months, and 39 percent lasting a year or more at the time results were analyzed. Examples of tumor types with an NTRK fusion that responded to larotrectinib include soft tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer and lung cancer.
The FDA granted Priority Review, Breakthrough Therapy designation and Orphan Drug designation to Vitrakvi. The approval of Vitrakvi is granted to Loxo Oncology.
About Vitrakvi (larotrectinib)
Larotrectinib, is a CNS active TRK inhibitor designed to inhibit these proteins. TRK fusions can be found in many types of solid tumors and affect both children and adults. In the clinical trials that were the basis for this approval, larotrectinib showed clinical benefit across numerous unique tumor types, including lung, thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland and infantile fibrosarcoma.
About NTRK gene fusion
NTRK genes, which encode for TRK proteins, can become fused to other genes abnormally, that result in constitutively-activated chimeric TRK fusion proteins, which act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines. NTRK fusions are rare but occur in cancers arising in many sites of the body. Prior to this approval, there had been no treatment for cancers that frequently express this mutation, like mammary analogue secretory carcinoma, cellular or mixed congenital mesoblastic nephroma and infantile fibrosarcoma.
Note- Larotrectinib has been developed by Bayer and Loxo Oncology, Inc.; Bayer submitted a Marketing Authorization Application in the European Union in August 2018 and additional filings in other countries are underway. Larotrectinib will be available in the U.S. market in oral capsules as well as a liquid formulation for adults and children.
Footnotes
1 https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626710.htm
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