The MARIPOSA trial marks a major step in evolving first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). This phase III study compared the combination of amivantamab (a bispecific EGFR-MET antibody) and lazertinib (a third-generation EGFR-TKI) to osimertinib monotherapy. Results showed that the combination significantly improved progression-free survival (PFS), with a median PFS of 23.7 months versus 16.6 months for osimertinib alone. On subsequent analysis presented in ELCC 2025, the combination of amivantamab + lazertinib also showed overall survival benefit in favor of the combination vs. single agent osimertinib (Hazard Ratio for death 0.75 (95% CI 0.61–0.92; P < 0.005)
While the combination was associated with higher rates of rash and infusion-related reactions, overall toxicity was manageable with supportive care and dose adjustments. Importantly, early signals suggest that the combination may delay the emergence of resistance mutations — a critical need in EGFR-driven disease.
This study highlights the growing role of combination targeted therapy in lung cancer and raises important questions about how to best sequence EGFR therapies. Ongoing research will further clarify its role, particularly in patients with brain metastases
