
The treatment of non–small cell lung cancer (NSCLC) harboring EGFR mutations has transformed with the introduction of targeted therapies. Despite the success of third-generation tyrosine kinase inhibitors (TKIs) such as osimertinib (Tagrisso; AstraZeneca), acquired resistance remains a challenge for most patients, limiting the durability of responses and ultimately driving disease progression.
Against this backdrop, updated findings from the phase 3 MARIPOSA trial (NCT04487080) were presented at the 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain, highlighting the potential of a dual-targeted strategy using the bispecific antibody amivantamab (Rybrevant; Janssen Biotech) in combination with the third-generation TKI lazertinib (Lazcluze; Janssen Biotech). The data show that this combination significantly reduces the emergence of resistance mechanisms compared with osimertinib, while also extending survival in patients with EGFR exon 19 deletions (ex19del) or exon 21 L858R substitution mutations.
Key Takeaways
- The MARIPOSA trial demonstrates that amivantamab plus lazertinib significantly reduces resistance and extends survival in EGFR-mutated NSCLC compared to osimertinib.
- Dual inhibition of EGFR and MET by amivantamab and lazertinib addresses resistance mechanisms like MET amplification and EGFR mutations, offering a new standard of care.
- The combination therapy is globally approved and recommended as a first-line treatment for EGFR ex19del– or L858R-mutated advanced NSCLC.
- Safety profiles of amivantamab plus lazertinib are consistent with known toxicities, with ongoing studies refining supportive care strategies to manage adverse events.
References:
Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) prevents acquiredresistance versus osimertinib in first-lineEGFR-mutated non-small cell lung cancer. News release. Johnson & Johnson. September 6, 2025. Accessed September 8, 2025. https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-prevents-acquired-resistance-versus-osimertinib-in-first-line-egfr-mutated-non-small-cell-lung-cancer-302548296.html
Aamivantamab and lazertinib combination therapy versus osimertinib in locally advanced or metastatic non-small cell lung cancer (MARIPOSA). Clinicaltrials.gov. Updated August 19, 2025. Accessed September 8, 2025. https://www.clinicaltrials.gov/study/NCT04487080
Read full article: https://www.ajmc.com/view/updated-mariposa-data-highlight-clinical-impact-of-upfront-dual-inhibition-in-egfr-nsclc







