On October 23, 2020, the FDA approved FoundationOne CDx to be used as a companion diagnostic for larotrectinib (Vitrakvi; Bayer), a drug currently approved by the FDA for the treatment of adult 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 following treatment.
On November 26, 2018, the FDA granted accelerated approval to larotrectinib, a selective tropomyosin receptor kinase inhibitor, based on the results of 3 multicenter, open-label, single-arm clinical trials: LOXO-TRK-14001, SCOUT, and NAVIGATE. Identification of positive NTRK gene fusion status was prospectively determined in local laboratories using next-generation sequencing or fluorescence in situ hybridization (FISH). NTRK gene fusions were inferred in 3 pediatric patients with infantile fibrosarcoma who had a documented ETV6 translocation by FISH. The major efficacy outcome measures were overall response rate and response duration, as determined by a blinded independent review committee according to RECIST v1.1.
The FoundationOne CDx assay approval as a companion diagnostic for larotrectinib was based on the retrospective testing with FoundationOne CDx of available tumor tissue samples from patients enrolled in the 3 clinical trials that supported the accelerated approval of larotrectinib. Efficacy for larotrectinib was shown to be maintained in patients with confirmed NTRK fusion–positive results by FoundationOne CDx.
“Taking a comprehensive and validated approach to genomic testing is critical for all advanced cancer patients, but especially for those harboring rare mutations that can be missed with alternative testing methods,” said Brian Alexander, MD, MPH, Chief Medical Officer at Foundation Medicine, in a company press release. “Not only will this approval improve access to genomic testing and reinforce the role it plays in rare cancers, but it also confirms the incredible progress made toward tumor-agnostic cancer care. We’re proud of the impact this will have on NTRK fusion–positive cancer patients.”