Multinational phase 1-2 study of mobocertinib for platinum-pretreated mNSLCL with EGFR exon 20 insertion mutations

Insertion mutations in EGFR exon 20 occur in 4% to 12% of EGFR-mutated NSCLCs. Most patients with EGFRex20ins-positive mNSCLC receive first-line platinum-based chemotherapy but typically develop progressive disease within 6 months. The EGFR TKIs afatinib, erlotinib, and gefinitib have limited activity in these patients. Monocertinib is a first-in-class, potent, oral, irreversible TKI designed to selectively target in-frame EGFRex20ins mutations in NSCLC. A multinational phase 1-2 study found that mobocertinib was associated with clinically meaningful benefit in patients with previously treated mNSCLC with EGFRex20ins mutations. The safety profile was manageable.