FDA, European Medicines Agency Accept Regulatory Submissions for Review of Dacomitinib

Pfizer announced the U.S. Food and Drug Administration (FDA) accepted the company’s New Drug Application and granted priority review for dacomitinib, a pan-human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations. The European Medicines Agency has also accepted the Marketing Authorization Application for dacomitinib for the same indication.

The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in September 2018.

"While significant progress has been made in the treatment of patients with non-small cell lung cancers harboring EGFR-activating mutations, it remains a challenging disease and new treatment options are needed," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "In the pivotal clinical trial that supports these applications, dacomitinib showed clinically meaningful improvement in progression-free survival over gefitinib, one of the first EGFR-targeted therapies to demonstrate activity in this disease. These filing acceptances are an important step toward increasing treatment options for patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer."

Dacomitinib is the second investigational Pfizer lung cancer medicine to receive regulatory acceptance within two months, reinforcing Pfizer’s commitment to patients with NSCLC where there continues to be a significant unmet need.

The submissions are based on results from the Phase 3 ARCHER 1050 study, a global head-to-head trial investigating dacomitinib (n=227) compared to gefitinib (n=225) that showed dacomitinib may offer a clinically meaningful improvement over gefitinib. Patients that received dacomitinib in the study experienced a median progression-free survival (PFS) of 14.7 months compared with 9.2 months in patients treated with gefitinib, as measured by Blinded Independent Central Review (BICR). This difference represented a 41 percent reduction in the risk of disease progression or death for patients treated with dacomitinib compared with gefitinib (HR = 0.59 [95% CI: 0.47,0.74], p <0.0001) as a first-line treatment in locally advanced or metastatic NSCLC with EGFR-activating mutations.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%), and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in 2 percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to 7 percent for gefitinib.

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