EGFR-mutated NSCLC is a biomarker-defined subtype of non-small-cell lung cancer characterized by activating EGFR mutations that can confer sensitivity to EGFR tyrosine kinase inhibitors. This subtype is more common in adenocarcinoma and in never-smokers or light smokers. Molecular testing is central to treatment selection.
The FDA approved once-monthly subcutaneous amivantamab with lazertinib for first-line EGFR-mutated advanced NSCLC. PALOMA-2 showed high response rates and no new safety signals.
The antibody-drug conjugate sacituzumab tirumotecan demonstrated significant survival benefits in pretreated EGFR-mutated NSCLC, with median overall survival of 20.0 months versus 13.5 months for docetaxel. The treatment also showed superior progression-free survival and objective response rates with a favorable safety profile compared to chemotherapy.
The FDA approved subcutaneous amivantamab for EGFR-mutated NSCLC in December 2025 based on phase 3 PALOMA-3 trial data showing noninferior efficacy with reduced infusion reactions and 5-minute administration time. The formulation decreases infusion-related reactions from 66% to 13% and improves patient convenience and quality of life. Recent MARIPOSA trial updates show amivantamab plus lazertinib extends median overall survival by at least 12 months versus osimertinib monotherapy.
The FDA has approved a new monthly dosing schedule for Johnson & Johnson's Rybrevant Faspro combined with Lazcluze for first-line treatment of advanced EGFR-mutated non-small cell lung cancer, allowing patients to transition to monthly dosing as early as week five.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07363252 |
Investigation of REcurrence Mechanisms to Adjuvant osimertINib in Radically Resected EGFR-mutated NSCLC Patients |
RECRUITING | |
| NCT06816992 |
ORIC-114 in Combination With Subcutaneous Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC |
RECRUITING | PHASE1 |
| NCT05241873 |
(Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations |
TERMINATED | PHASE1 |
