FDA Approves Companion Diagnostic for EGFR Therapies for Exon 19 Deletions and Exon 21 Alterations in NSCLC - Targeted Oncology

The FDA has approved the FoundationOne CDx as a companion diagnostic to identify patients with non–small cell lung cancer with tumors that harbor EGFR exon 19 deletions or exon 21 substitutions.

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

"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."

This CDx is an in vitro diagnostic device designed to detect substitutions, insertion, and deletion alterations. Additionally, it can copy number alterations in a total of 324 genes, and identify select gene rearrangements and genomic signatures. This includes microsatellite instability and tumor mutational burden, which is done through examining DNA extracted from formalin-fixed, paraffin-embedded tumor tissue samples.

This is the first FDA-approved tissue-based broad companion diagnostic that is clinically and analytically validated for all solid tumors. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions, and loss of heterozygosity (LOH) for patients with ovarian cancer.

The companion diagnostic can be used with various therapies approved for those with NSCLC whose tumors harbor EGFR exon 19 deletions and EGFR exon 21 L858R alterations including erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), and osimertinib (Tagrisso).²

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

The FDA also greenlit the use of the diagnostic to help identify patients with metastatic NSCLC whose tumors harbor MET exon 14 skipping mutations and who could derive benefit from treatment with capmatinib (Tabrecta) in July 2021.³

In May 2020, the regulatory agency had approved the use of capmatinib in these patients based on the results of the phase 2 GEOMETRY mono-1 study (NCT02414139).^4,5 This study evaluated the antitumor activity of the oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced NSCLC as well as the safety and pharmacokinetics of capmatinib.

Findings revealed the agent demonstrated a clinically meaningful objective response rate of 67.9% (95% CI, 47.6%-84.1%) per independent review.⁴ Capmatinib demonstrated an overall response rate of 68% and 41% in treatment-naive and previously treated METex14 patients, respectively.

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. Kucharczuk CR, Ganetsky A, Vozniak JM. Drug-Drug Interactions, Safety, and Pharmacokinetics of EGFR Tyrosine Kinase Inhibitors for the Treatment of Non–Small Cell Lung Cancer. J Adv Pract Oncol. 2018 Mar; 9(2): 189–200.

3. 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

4. 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/3uaQluN

5. Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1). Clinicaltrials.gov. Accessed March 17, 2022. https://www.clinicaltrials.gov/ct2/show/NCT02414139