REZILIENT3: randomized phase III study of first-line zipalertinib plus chemotherapy in patients with <i>EGFR</i> exon 20 insertion-mutated NSCLC

There remains a significant unmet need for effective and tolerable treatments for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (<i>EGFR</i>) exon 20 insertion (ex20ins) mutations in the first-line setting. First and later generation EGFR tyrosine kinase inhibitors (TKIs) have shown efficacy for common <i>EGFR</i> mutations; however, their effectiveness against ex20ins mutations is limited, and platinum-based chemotherapy remains part of the standard of care. Data suggest that combining chemotherapy with EGFR inhibitors offers promise for <i>EGFR</i> ex20ins-mutated NSCLC. REZILIENT3 is an ongoing phase III study evaluating the efficacy and safety of zipalertinib (an orally available, irreversible EGFR-TKI) plus first-line standard-of-care platinum-based chemotherapy with chemotherapy alone in previously untreated patients with nonsquamous NSCLC harboring <i>EGFR</i> ex20ins mutations.<b>Clinical Trial Registration:</b> NCT05973773 (ClinicalTrials.gov).