Brief Report: Aumolertinib as a Switch Therapy in Osimertinib-Intolerant NSCLC-The ACTIVE Trial

Third-generation EGFR- tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for EGFR-mutant advanced NSCLC. Prospective data on toxicity-driven switching to alternative third-generation TKIs for intolerant patients remain limited.

In this prospective, multicenter, single-arm phase II trial (NCT04882345), patients with EGFR-mutant advanced NSCLC who developed grade 2 or higher hematologic toxicities or increase in alanine transaminase (ALT) or aspartate transaminase (AST), or grade 3 or higher nonhematologic adverse events (AEs) (excluding ALT or AST increase) on osimertinib received aumolertinib 110 mg once daily after AEs recovered to grade 1 or lower. The primary end point was the 3-month conversion success rate (absence of disease progression, grade ≥2 hematologic AEs or increase in ALT or AST, and grade ≥3 nonhematologic AEs).

Of the 40 enrolled patients, 39 received aumolertinib, and 34 were evaluable for the primary end point. The 3-month conversion success rate was 70.6% (95% confidence interval: 52.5-84.9) in the evaluable population, with 78.9% in nonhematologic toxicity and 60.0% in hematologic toxicity subgroups. Median postswitch progression-free survival was 11.6 months, and the 3-year postswitch overall survival rate was 52.4%. Treatment-related AEs occurred in 69.2% of patients (grade ≥3: 15.4%), with no aumolertinib discontinuation or death.

This prospective trial suggests that switching to aumolertinib achieves sustained efficacy and manageable safety in osimertinib-intolerant EGFR-mutant advanced NSCLC, supporting toxicity-driven EGFR-TKI switching as a feasible clinical strategy.