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Companion Diagnostic Approved to Identify NTRK Fusions in Patients Eligible for Larotrectinib

FoundationOne® CDx test.

The FDA has approved FoundationOne® CDx (Foundation Medicine, Inc.) as a companion diagnostic device to identify neurotrophic receptor tyrosine kinase (NTRK) fusions in patients with solid tumors in order to determine eligibility for treatment with larotrectinib (Vitrakvi®, Bayer Healthcare Pharmaceuticals, Inc.). FoundationOne is a next-generation sequencing (NGS)-based in vitro diagnostic device previously approved to determine eligibility for more than 20 other FDA-approved targeted therapies.

In November 2018, larotrectinib was granted accelerated approval for the treatment of adult and pediatric patients with NTRK fusion-positive solid tumors, including melanoma, soft-tissue sarcoma, infantile fibrosarcoma, and thyroid, lung, breast, colorectal, and salivary gland cancers. Larotrectinib is indicated for patients whose disease is metastatic or who are unfit for surgical resection, who have progressive disease or no satisfactory alternative treatment options, and who have no known acquired resistance mutations. The approval of larotrectinib was based on three clinical trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

"NTRK1, NTRK2, and NTRK3 encode the tropomyosin receptor kinase (TRK) proteins TRKA, TRKB, and TRKC, respectively," wrote the authors of a pooled analysis of the three trials, led by first author Alexander Drilon, MD, Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. "TRK fusions lead to overexpression of the chimeric protein, resulting in constitutively active, ligand-independent downstream signaling. Biologic models and early clinical evidence suggest that these fusions lead to oncogene addiction regardless of tissue of origin, and, in aggregate, may be implicated in up to 1% of all solid tumors."

The three trials enrolled a total of 55 patients with NTRK fusion-positive solid tumors, the most common being salivary gland cancer (22%), soft-tissue sarcoma (20%), infantile fibrosarcoma (13%), and thyroid cancer (9%). In the pooled analysis, larotrectinib produced an overall response rate of 75% according to independent review and 80% according to investigator assessment. Median duration of response and median progression-free survival were not reached. At a median follow-up of 9.4 months, 86% of patients who experienced a response were still receiving treatment or had undergone curative surgery. FoundationOne® CDx was used for retrospective testing of available tumor tissue samples from patients enrolled in the three trials.

"Many patients with rare conditions, like NTRK fusion-positive cancer, have limited treatment options and poor access to targeted therapies," commented Susan Spinosa, Co-Chair and patient founder of NTRKers, an organization dedicated to supporting patients with NTRK fusion-positive tumors. "This companion diagnostic approval is a critical step forward in addressing this challenge, as it provides this patient population with broader access to comprehensive genomic testing and appropriate treatment options."

For More Information

US Food and Drug Administration (2020). FDA approves companion diagnostic to identify NTRK fusions in solid tumors for Vitrakvi. Available at: https://www.fda.gov/drugs/fda-approves-companion-diagnostic-identify-ntrk-fusions-solid-tumors-vitrakvi?utm_medium=email&utm_source=govdelivery

Foundation Medicine, Inc. (2020). FoundationOne® CDx receives FDA-approval as a companion diagnostic for VITRAKVI® (larotrectinib) to identify patients with NTRK fusions across all solid tumors. Available at: https://www.foundationmedicine.com/press-releases/c90da36c-205d-4b8d-9848-dfcb970da47a

Drilon A, Laetsch TW, Kummar S, et al (2018). Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med, 378:731-739. DOI:10.1056/NEJMoa1714448

Vitrakvi® (larotrectinib) prescribing information (2018). Bayer Healthcare Pharmaceuticals, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf

Image credit: US Food & Drug Administration

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