Late-line Real-world Outcomes of Amivantamab Plus Lazertinib After EGFR-TKI Failure in EGFR-Mutated Non-Small Cell Lung Cancer

Abstract Background Real-world evidence on amivantamab plus lazertinib after EGFR tyrosine kinase inhibitor (EGFR-TKI) failure remains limited, particularly in later-line settings. We evaluated the clinical outcomes, safety, and exploratory genomic findings of this regimen in a single-institution cohort. Methods We retrospectively reviewed patients with advanced or recurrent EGFR -mutated non-small cell lung cancer, excluding EGFR exon 20 insertion mutations, who initiated amivantamab plus lazertinib after EGFR-TKI therapy at a single institution between July 2025 and May 2026. First-line patients were excluded. Time to treatment failure (TTF), adverse events, and comprehensive genomic profiling results from post-EGFR-TKI failure tumor biopsy specimens were evaluated. Results Eighteen patients were included. The median treatment line was 3.5, and 16 patients had received osimertinib. Among 13 response-evaluable patients, the best overall response was partial response in 1 patient, stable disease in 4 patients, non-CR/non-PD in 6 patients, and progressive disease in 2 patients, yielding an objective response rate of 7.7% and a disease control rate of 84.6%. The median TTF was 8.5 months. Infusion-related reactions occurred in 5 patients, with no grade 3 or higher events. Grade 3 or higher adverse events occurred in 8 patients, and adverse event-related discontinuation occurred in 1 patient. Comprehensive genomic profiling was available in 6 patients and revealed EGFR amplification in 3 patients, MET amplification in 1 patient, and EGFR C797S in 1 patient. Conclusion Amivantamab plus lazertinib showed disease control and manageable safety in a later-line real-world cohort after EGFR-TKI failure. Exploratory genomic findings demonstrated molecular heterogeneity, warranting further study.