Oral Tyrosine Kinase Inhibitor for EGFR Exon 20-Insertion-Positive NSCLC

Mobocertinib is a first-in-class irreversible tyrosine kinase inhibitor that was designed to selectively target in-frame EGFR exon 20 insertion (EGFRex20ins) mutations in non–small-cell lung cancer (NSCLC). In a multicenter phase 1/2 nonrandomized study, 114 patients with EGFRex20ins-positive NSCLC previously treated with platinum-based chemotherapy received mobocertinib (160 mg once daily) until disease progression or unacceptable toxicity.

At a median 14.2 months' follow up, the objective response rate by independent review — the primary endpoint — was 28% (95% confidence interval, 20%–37%). An additional 50% of patients had stable disease, for a disease control rate of 78%. The median duration of response was 17.5 months (95% CI, 7.4–20.3 months), median progression-free survival was 7.3 months (95% CI, 5.5–9.2 months), and median overall survival was 24.0 months (95% CI, 14.6–28.8 months). The most common treatment-related adverse events of any grade were diarrhea (91%), rash (45%), and paronychia (38%). Grade >3 adverse events occurred in 69% of patients and were considered treatment-related in 47%. Adverse events led to dose reduction in 25% of patients and to treatment discontinuation in 17%, most commonly owing to diarrhea (4%), nausea (4%), vomiting (2%), decreased appetite (2%), and stomatitis (2%).