Foundation Medicine’s CGP Test FDA Approved as Companion Diagnostic for Bayer’s Tumor Agnostic Therapy
By Eduardo Longoria & Rajaneesh K. Gopinath, Ph.D.
On October 23rd, Cambridge, MA-based Foundation Medicine, Inc. (F.M.I) announced that it had received FDA approval for FoundationOne®CDx as a companion diagnostic for Bayer’s VITRAKVI® (larotrectinib). VITRAKVI® was originally FDA-approved in November 2018 to treat adult and pediatric patients whose solid tumors have a specific biomarker, a neurotrophic receptor tyrosine kinase (NTRK) gene fusion that does not harbor a known acquired resistant mutation to NTRK inhibitors. Originally developed by Loxo Oncology, the tropomyosin kinase receptor was indicated for the treatment of metastatic solid tumors, where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments.
NTRK fusion-positive Cancers
NTRK gene fusions are formed when an NTRK gene breaks off from one chromosome and fuses with another. This fusion leads to altered TRK fusion proteins that cause cancer cells to grow as NTRK fusion-positive cancers. NTRK fusions are often found in rare cancer types, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma. However, they can also occur across more common types, including cancers of the brain, head, and neck, thyroid, soft tissue, lung, and colon.
“Many patients with rare conditions, like NTRK fusion-positive cancer, have limited treatment options and poor access to targeted therapies,” said Susan Spinosa, co-chair and patient founder of the NTRKers. “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.”
FoundationOne CDx is an in vitro diagnostic device that uses next-generation sequencing. It detects substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and gene rearrangements as well as genomic signatures, including microsatellite instability (MSI) and tumor mutational burden (TMB).
FoundationOne CDx is the first FDA-approved tissue-based comprehensive genomic profiling (CGP) assay that is clinically and analytically validated for solid tumors. In March 2018, it also became the first FDA approved broad companion diagnostic with Medicare coverage. The NGS-based assay is now approved to detect NTRK1/2/3 fusions across all solid tumor types and identify patients who may be appropriate for treatment with VITRAKVI®. This is the second time the agency has approved FoundationOne CDx as a companion diagnostic for an approved tumor-agnostic therapy (the first was for Merck’s Keytruda in June). It is currently authorized as a companion diagnostic for more than 20 targeted therapies overall. Besides FoundationOne CDx, the company also recently received FDA approval for its liquid biopsy test, FoundationOne Liquid.
“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, M.D., M.P.H., Chief Medical Officer at FMI. “This companion diagnostic approval is a critical step forward in addressing the challenge of NTRK fusion-positive patients having limited treatment options and a lack of access to targeted therapies.”
Clinical Trial Data
VITRAKVI® was approved based on the data of three multicenter, open-label, and single-armed clinical trials, LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431). The biomarker status was determined using next-generation sequencing (NGS) or fluorescence in situ hybridization (FISH). The major efficacy outcome measures were overall response rate (ORR) and response duration. The drug demonstrated an overall response rate (ORR) of 75% (N=55) (95% CI, 61%, 85%), across various tumor types, including soft tissue sarcoma, salivary gland, thyroid, lung, melanoma, colon, appendix, breast and pancreas among others. It also registered a 22 percent complete response (CR) rate.
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