Zipalertinib Shows Sustained EGFR Exon 20 Inhibition, Yielding similar ORR to SOC in Pre-Treated NSCLC, but Better Tolerability.

Zipalertinib (zipa, CLN-081, TAS6417) is a novel EGFR TKI designed for NSCLC patients with EGFR exon 20 insertion (ex20ins) who progressed on platinum-based chemotherapy. In the phase 2b REZILIENT1 study of 176 patients, zipalertinib achieved a confirmed ORR of 35.2%, mDoR 8.8 months, mPFS 9.5 months post–platinum chemotherapy with/without prior amivantamab. Responders without prior amivantamab reached an ORR of 40%, while those with prior amivantamab had ORRs of 30.0% (without additional ex20ins therapy) and 14.3% (with other ex20ins agents). The majority of TEAEs were Grade 1 or 2. For comparison, the current standard of care for pretreated non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations with amivantamab monotherapy has an ORR of 40% and an mPFS of 8.3 months with grade 3 or higher adverse events of 35% to 44% in the CHRYSALIS study.