FDA Green Lights Companion Diagnostic for EGFR Therapies Targeting Exon 19 Deletions or Exon 21 Alterations in NSCLC

Mia Levy, MD, PhD

The FDA has approved the FoundationOne CDx for use as a companion diagnostic to determine which patients with non–small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) substitutions may derive benefit from EGFR TKIs that have been greenlit by the agency for this indication.¹

The in vitro diagnostic device was designed to detect substitutions, insertion, and deletion alterations, as well as copy number alterations in a total of 324 genes. The test can also identify select gene rearrangements and genomic signatures such as microsatellite instability and tumor mutational burden by examining DNA extracted from formalin-fixed, paraffin-embedded tumor tissue samples.

“Cancer treatment decision making is growing more complex as we learn more about the mutations that drive cancers to grow and new treatments become available to target those changes,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a press release. “We believe securing a third group companion diagnostic approval for FoundationOne CDx is another critical step toward simplifying the decision-making process for oncologists and their patients by allowing them to uncover all FDA-approved treatment options for this indication through 1 test.”

The therapies that are approved for those with NSCLC whose tumors harbor EGFR exon 19 deletions and EGFR exon 21 L858R alterations, and for which the companion diagnostic is indicated, include afatinib (Gilotrif), gefitinib (Iressa), osimertinib (Tagrisso), and erlotinib (Tarceva).

The companion diagnostic is also indicated for use in identifying patients with EGFR exon 20 T790M alterations who might benefit from osimertinib; those with ALK rearrangements who may be candidates for alectinib (Alecensa), brigatinib (Alunbrig), crizotinib (Xalkori), or ceritinib (Zykadia); and those with BRAF V600E mutations who should receive dabrafenib (Tafinlar) in combination with trametinib (Mekinist).

In July 2021, the FDA approved the use of the diagnostic to assist in the identification of patients with metastatic NSCLC whose tumors harbor MET exon 14 skipping mutations and who could derive benefit from treatment with capmatinib (Tabrecta).² Almost a year prior, in May 2020, the regulatory agency had greenlit capmatinib for use in these patients based on findings from the phase 2 GEOMETRY mono-1 study (NCT02424139), in which the agent induced an objective response rate of 67.9% (95% CI, 47.6%-84.1%) per independent review.³

References

1. US FDA approves FoundationOne CDx as a companion diagnostic for EGFR therapeutics targeting exon 19 deletions or exon 21 substitutions in non-small cell lung cancer. News release. Foundation Medicine; March 17, 2022. Accessed March 17, 2022. https://bit.ly/3KQYk6W
2. Foundation Medicine expands indication for FoundationOne Liquid CDx to be used as companion diagnostic for TABRECTA (capmatinib). News release. Foundation Medicine, Inc.; July 15, 2021. Accessed March 17, 2022. https://bwnews.pr/3hJ54rv
3. Novartis announces FDA approval of MET inhibitor Tabrecta for metastatic non-small cell lung cancer with METex14. News release. Novartis; May 6, 2020. Accessed March 17, 2022. https://bit.ly/2SIEmTc