FDA Greenlights Companion Diagnostic for BRAF Inhibitors in Melanoma

FDA

The FDA has approved FoundationOne CDx for use as a companion diagnostic for 2 groups of current a future regulatory-approved treatments in melanoma, including single-agent BRAF inhibitors targeting BRAF V600E mutations and BRAF/MEK combination regimens targeting BRAF V600E or V600K mutations.¹

The companion diagnostic will be used for selecting appropriate patients for the combination of encorafenib (Braftovi) and binimetinib (Mektovi), as well as dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with melanoma.

In the future, the assay will automatically become a companion diagnostic for BRAF inhibitors that are greenlit by the regulatory agency, if they fall under these groups.

“As the first group therapy approval for any comprehensive genomic profiling test, this milestone reinforces our dedication to pioneering advances that expand the power of genomic testing in cancer care,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a press release. “This approval will allow oncologists to uncover all possible FDA-approved treatment options for these indications through just 1 test, providing more insights for physicians and patients, more efficiently than ever before.”

A next-generation sequencing assay, FoundationOne CDx was designed to detect substitutions, insertions, and deletion alterations, as well as copy number alterations, in a total of 324 genes, select gene rearrangements, and genomic signatures such as microsatellite instability and tumor mutational burden. It does this by using DNA that is extracted from formalin-fixed, paraffin-embedded tumor tissue specimens.

The test is intended to provide tumor mutation profiling and to be utilized by professionals in accordance with established oncology guidelines for patients with solid malignant neoplasms.

The assay is approved for use as a companion diagnostic spanning several indications.2 In melanoma, the test is used to select patients who harbor BRAF V600E mutations and may benefit from single-agent dabrafenib or vemurafenib (Zelboraf), or those with BRAF V600E or V600K mutations who should receive trametinib or cobimetinib (Cotellic) in combination with vemurafenib.

In non–small cell lung cancer, it is used to detect EGFR exon 19 deletions and EGFR exon 21 L858R alterations that correspond with approved agents such as afatinib (Gilotrif), gefitinib (Iressa), osimertinib (Tagrisso), and erlotinib (Tarceva). It is indicated for the detection of EGFR exon 20 T790M alterations and osimertinib; ALK rearrangements and alectinib (Alecensa), brigatinib (Alunbrig), crizotinib (Xalkori), and ceritinib (Zykadia); BRAF V600E mutations and dabrafenib plus trametinib; and MET single nucleotide variants and indels that result in MET exon 14 skipping mutations and capmatinib (Tabrecta).

In breast cancer, the test is used to detect ERBB2 amplification and identify patients eligible to receive trastuzumab (Herceptin), ado-trastuzumab emtansine (Kadcyla), and pertuzumab (Perjeta); as well as several PIK3CA alterations to determine who should receive alpelisib (Piqray). In colorectal cancer, the assay is greenlit for use in the identification of KRAS wild-type disease (absence of mutations in codons 12 and 13) so that cetuximab (Erbitux) can be leveraged, as well as KRAS (absence of mutations in exons 2, 3, and 4) and NRAS wild-type (absence of mutations in exons 2, 3, and 4) so that panitumumab (Vectibix).

In ovarian cancer, the test has been greenlit for use as a companion diagnostic for olaparib (Lynparza) and rucaparib (Rubraca) for patients whose tumors harbor BRCA1/2 alterations. In cholangiocarcinoma, it is used to detect FGFR2 fusions and rearrangements so that pemigatinib (Pemazyre) or infigratinib (Truseltiq) can be utilized.

In prostate cancer, it is a companion diagnostic for olaparib, in that it helps to detect homologous recombination repair gene alterations. Lastly, in solid tumors, it is used to detect tumor mutational burden so that pembrolizumab (Keytruda) may be leveraged, as well as NTRK1/2/3 fusions, so that larotrectinib (Vitrakvi) may be administered to eligible patients.

“This approval represents an innovative, more efficient regulatory approach that simplifies the companion diagnostic approval process for biopharma companies developing BRAF inhibitor therapeutics, while maintaining rigor and high-quality standards,” according to Foundation Medicine, Inc.

References

1. FoundationOne CDx receives FDA approval as a companion diagnostic for BRAF inhibitor therapeutics in melanoma. News release. Foundation Medicine, Inc.; December 8, 2021. Accessed December 8, 2021. https://bwnews.pr/3rOa43J
2. FoundationOne CDx. Foundation Medicine website. Accessed December 8, 2021. https://bit.ly/3qE4r5q