The phase III MARIPOSA trial was a head-to-head comparison of the EGFR tyrosine kinase inhibitor osimertinib and the combination of the bispecific EGF receptor–directed and MET receptor–directed monoclonal antibody amivantamab-vmjw and the EGFR tyrosine kinase inhibitor lazertinib in the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations. At the European Lung Cancer Congress (ELCC) 2025, investigators presented final survival data from this trial, showing significantly extended overall survival with the combination therapy over osimertinib alone.1 The median overall survival, which has not yet been reached, is projected to exceed 1 year beyond the median of 3 years observed with osimertinib. The MARIPOSA study had previously met its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival with amivantamab plus lazertinib vs osimertinib.
“The survival curve tells a clear story. Amivantamab plus lazertinib helps patients live longer, and the benefit keeps growing over time.”— NICOLAS GIRARD, MD, PhD
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“The survival curve tells a clear story. Amivantamab plus lazertinib helps patients live longer, and the benefit keeps growing over time,” said trial investigator Nicolas Girard, MD, PhD, Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine, Paris-Saclay University, France. “We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR-mutated non–small cell lung cancer.”
Key Results
The MARIPOSA trial enrolled 1,074 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations. At a median follow-up of 37.8 months, patients treated in the first-line setting with the chemotherapy-free regimen of amivantamab plus lazertinib had a significantly longer overall survival than did those who received osimertinib (hazard ratio [HR] = 0.75; 95% confidence interval [CI] = 0.61–0.92; P < .005). Median overall survival for the combination therapy has not yet been reached (95% CI = 42.9 months to not reached). In comparison, median overall survival for osimertinib-treated patients was 36.7 months (95% CI = 33.4–41.0 months), which was consistent with prior studies of osimertinib. A total of 66% of patients treated with amivantamab plus lazertinib were alive at 3.5 years vs 44% of patients treated with osimertinib.
In addition, multiple secondary endpoints were improved with amivantamab plus lazertinib vs osimertinib, including intracranial progression-free survival, intracranial duration of response, and intracranial overall response rate. Of note, the time to symptomatic disease progression (from treatment randomization to the onset of lung cancer symptoms) was longer with amivantamab plus lazertinib than with osimertinib (43.6 months vs 29.3 months; HR = 0.69; 95% CI = 0.57–0.83; P < .001).
As for the safety profile of the combination of amivantamab and lazertinib, it was consistent with the primary analysis. No new safety signals were identified with the additional follow-up. Most adverse events with the combination therapy have been reported early during treatment.2 Research findings suggest that implementing prophylactic measures during the first 4 months of treatment with these agents may significantly reduce the risk of skin reactions, infusion-related reactions, and venous thromboembolic events.2
DISCLOSURE: Dr. Girard has served as a consultant to Johnson & Johnson but has not been paid for any media work. For disclosures of the other study authors, visit cslide.ctimeetingtech.com.
REFERENCES
1. Yang JCH, Kim YJ, Lee SH, et al: Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced NSCLC: Final overall survival from the phase III MARIPOSA study. European Lung Cancer Congress 2025. Abstract 4O. Presented March 26, 2025.
2. Leighl NB, Akamatsu H, Lim SM, et al: Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor–mutated non–small cell lung cancer: Primary results from the phase III PALOMA-3 study. J Clin Oncol 42:3593-3605, 2024.
