Multinational phase 1-2a trial of zipalertinib for non-small cell lung cancer with EGFR exon 20 insertions

Although several agents targeting EGFR exon 20 insertions (ex20ins) have recently been approved, toxicities related to the inhibition of wild-type EGFR affect tolerabilty. Zipalertinib is an oral EGFR TKI with a novel pyrrolopyrimidine scaffold leading to enhance selectivity for EGFR ex20ins-mutant versus wild-type EGFR. A multinational phase 1-2a trial evaluated zipalertinib among patients with recurrent or metastatic EGFR ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy (median previous systemic therapies 2; range 1-9). Zipalertinib had promising antitumor activity, with an acceptable safety profile, including low frequency of diarrhea and rash.