The FoundationOne CDx (F1CDx) test received full U.S. Food and Drug Administration (FDA) approval. F1CDx is the first breakthrough-designated, next-generation sequencing–based in vitro diagnostic (IVD) test to detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type. Simultaneous to FDA approval, the Centers for Medicare & Medicaid Services (CMS) proposed coverage of the F1CDx. Th e test is the second IVD to be approved and covered aft er overlapping review by the FDA and CMS under the Parallel Review Program, which facilitates earlier access to innovative medical technologies for Medicare beneficiaries. (11/30)
The FDA is making several efforts to advance the development of innovative targeted drugs and enable increased and more timely availability of individualized treatment approaches. Two draft guidances have been released: “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease” and “Investigational IVD Devices Used in Clinical Investigations of Therapeutic Products.” Respectively, these guidance documents off er drug developers an approach for enrolling patients to targeted therapy trials based on the identifi cation of rare mutations when reasonable scientific evidence suggests the study drug could be effective for these mutations, and then clarifies the appropriate regulatory pathway for investigational in vitro devices used in clinical trials for therapeutic products. (For more on this topic, read the April edition’s FDA Corner.) (12/15)
The FDA has accepted a supplemental New Drug Application (sNDA) for the use of osimertinib in the first-line treatment of patients with metastatic NSCLC whose tumors have activating EGFR mutations (exon 19 deletions or exon 21 [L858R] substitution mutations). Osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor with clinical activity against central nervous system metastases. The FDA has granted osimertinib Priority Review status and previously granted it Breakthrough Therapy Designation in the first-line treatment of patients with metastatic EGFR mutation–positive (EGFRm) NSCLC. sNDA acceptance was based on progression-free survival data for previously untreated patients with locally advanced or metastatic EGFRm NSCLC in the phase III FLAURA trial. (12/18)
The European Commission has granted a marketing authorization for alectinib as monotherapy for the first-line treatment of adult patients with ALK positive advanced NSCLC. The approval is based on results from the phase III ALEX study, which showed alectinib significantly reduced the risk of disease worsening or death (progression-free survival) by 53% (HR = 0.47, 95% CI: 0.34-0.65, p < 0.001) compared to crizotinib. Th e study also showed that alectinib reduced the risk of tumors spreading to or growing in the brain or central nervous system compared to crizotinib by 84% (HR = 0.16, 95% CI: 0.10-0.28, p <0.001). (12/21)
The FDA granted approval to afatinib for a broadened indication in first-line treatment of patients with metastatic NSCLC whose tumors have nonresistant EGFR mutations as detected by an FDA-approved test. Approval was based on durable response in 21 of 32 patients with nonresistant EGFR mutations (S768I, L861Q, and/or G719X) other than exon 19 deletions or exon 21 L858R substitutions enrolled in one of three clinical trials. Of 21 responders, the proportion of patients with response duration of ≥12 months was 52%, and the proportion with response durations of ≥18 months was 33%. (1/12) ✦
