Multicenter phase 2 trial of aumolertinib as switch therapy in osimertinib-intolerant non-small cell lung cancer

Third-generation EGFR-TKIs are standard first-line therapy for EGFR-mutant advanced non-small cell lung cancer (aNSCLC). The multicenter phase 2 ACTIVE trial in China evaluated aumolertinib as switch therapy in aNSCLC patients who were intolerant to osimertinib. Patients who developed grade ≥ 2 hematologic toxicities or ALT/AST increase or grade ≥3 non-hematologic adverse events (AEs; excluding ALT/AST increase) on osimertinib received aumolertinib 110 mg once daily after AEs recovered to grade ≤ 1. The primary endpoint was the 3-month conversion success rate (absence of disease progression, grade ≥ hematologic AEs or ALT/AST increase, and grade ≥ 3 non-hematologic AEs). Of 40 enrolled patients, 39 received aulomertinib, and 34 were evaluable for the primary endpoint. The 3-month conversion success rate was 70.6% (95% CI 52.5-84.0) among all evaluable patients, with 78.9% in the non-hematologic toxicity subgroup and 60.0% in the hematologic toxicity subgroup. Median post-switch progression-free survival was 11.6 months, and the 3-year post-switch 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. The authors conclude that switching to aumolertinib achieves sustained efficacy and manageable safety in osimertinib-intolerant EGFR-mutant aNSCLC.