Larotrectinib Precision Cancer Medicine New Drug Application Submitted to FDA

Loxo Oncology has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring an NTRK gene fusion. This includes individuals with various sarcomas and fibrosarcomas.

Clinical data from three ongoing larotrectinib (LOXO-101) clinical trials in patients whose tumors harbor tropomyosin receptor kinase (TRK) fusions demonstrating a 76 percent confirmed objective response rate were recently published in the New England Journal of Medicine after an initial summary presentation at the American Society of Clinical Oncology in 2017.1,2

Larotrectinib received Breakthrough Therapy Designation from the FDA in July 2016, for the treatment of unresectable or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments.  Larotrectinib appears to deliver consistent and durable responses in TRK fusion patients across all ages with few side effects.

Rare Mutation

Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.  Larotrectinib targets theTRK fusion gene which occurs in some sarcomas and fibrosarcomas.

TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1NTRK2NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6LMNATPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors including sarcomas, fibrosarcomas, and gastrointestinal stromal tumors (GIST). TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

The larotrectinib TRK fusion story fulfills the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach. It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the standard sarcoma patient workup.

For additional information about the larotrectinib clinical trials, patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

Reference: 

  1. http://www.nejm.org/doi/full/10.1056/NEJMoa1714448?query=featured_home
  2. http://news.cancerconnect.com/larotrectinib-demonstrates-76-percent-response-rate-trk-fusion-adult-pediatric-cancers/

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