On September 15, 2021, the FDA accelerated the approval of mobocertinib (Exkivity; Takeda), an oral kinase inhibitor, for adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease progressed during or after platinum-based chemotherapy. Mobocertinib received breakthrough therapy and orphan drug designations for this indication.
On the same day, the FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic test for the identification of candidates for mobocertinib therapy.
“EGFR Exon 20 insertion-positive NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, said in a statement. “The approval of Exkivity (mobocertinib) marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses.”
The FDA approved mobocertinib based on Study 101, an international, nonrandomized, open-label, multicohort clinical trial of 114 patients with locally advanced or metastatic NSCLC and EGFR exon 20 insertion mutations, whose disease progressed during or after platinum-based chemotherapy. Patients received oral mobocertinib 160 mg daily, until disease progression or intolerable adverse events.
The main efficacy measures were overall response rate (ORR) and response duration. The ORR was 28% (95% confidence interval [CI], 20%-37%), with a median response duration of 17.5 months (95% CI, 7.4-20.3).
The most common (>20%) adverse reactions were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. Mobocertinib was approved with boxed warnings about risk for corrected QT prolongation and Torsades de Pointes, interstitial lung disease or pneumonitis, cardiac adverse reactions, and diarrhea.
Continued approval of this indication may be contingent on confirmatory data from a clinical trial.