New Indication: Amivantamab-Lazertinib for First Line Advanced EGFR-Mutated NSCLC

The MARIPOSA trial demonstrated that amivantamab-lazertinib significantly improved overall survival compared to osimertinib in EGFR-mutated advanced NSCLC in 1st line setting, with a 25% reduction in the risk of death. However, amivantamab-lazertinib was associated with a higher incidence of grade 3 or higher adverse events, particularly venous thromboembolism and infusion-related reactions.


  • Study

    Randomized, international, phase 3 trial [MARIPOSA, NCT04487080]
    Previously untreated EGFR-mutated (exon 19 deletion or L858R substitution) advanced NSCLC
    Amivantamab–Lazertinib (n=429) vs Osimertinib (n=429) vs Lazertinib (not summarized)



  • Efficacy

    3-yr OS: 60% vs 51%
    mOS: NE vs 36.7 mos (HR 0.75 [0.61-0.92])
    Median time to first subsequent therapy: 30.3 mos vs 24.0 mos (HR 0.76 [0.64-0.90])
    Intracranial PFS: 25.4 mos vs 22.2 mos (HR 0.79 [0.61-1.02])



  • Safety

    Grade >=3 AEs: 80% vs 52%
    Serious AEs: 55% vs 41%
    Venous thromboembolism: 40% vs 11%
    Infusion-related reaction: 65% vs 0%



    N Engl J Med. Published online September 7, 2025.


    Yang JCH, Lu S, Hayashi H

    New Indication: Amivantamab-Lazertinib for First Line Advanced EGFR-Mutated NSCLC


    http://doi.org/10.1056/NEJMoa2503001

    Reviewed by Ulas D. Bayraktar, MD on Oct 13, 2025

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