Gadgeel on MARIPOSA Trial Updates in EGFR+ NSCLC

Shirish M. Gadgeel, MD, chief of the division of hematology/oncology at Henry Ford Cancer Institute, Henry Ford Health in Detroit, Michigan, provides and overview of the MARIPOSA trial (NCT04487080) which evaluated the combination of lazertinib (Lazcluze) and amivantamab-vmjw (Rybrevant) vs osimertinib (Tagrisso) in treatment-naive patients with EGFR-mutated advanced or metastatic non­–small cell lung cancer (NSCLC).

The MARIPOSA study was conducted in patients with NSCLC harboring EGFR mutations. Investigators sought to assess the combination of amivantamab and lazertinib compared with the standard of care, osimertinib, in this patient population. A total of 1074 patients were enrolled and randomized in a 2:2:1 fashion to receive amivantamab plus lazertinib, lazertinib alone, or osimertinib alone. The primary end point of this study was progression-free survival (PFS).

Earlier results from the study showed that at a median follow-up of 31.1 months, amivantamab plus lazertinib outperformed osimertinib across multiple efficacy end points.¹ The intracranial PFS was significantly improved with the combination at 38% vs 18% with standard of care at 3 years. A promising trend in overall survival (OS) was also demonstrated, with the median OS not yet reached for the combination compared with 37.3 months for osimertinib.

Now, new data presented at the 2025 European Lung Cancer Congress (ELCC), showed that at a median follow-up of 37.8 months, patients treated with the chemotherapy-free regimen of first-line amivantamab plus lazertinib had a significantly longer OS vs those given osimertinib (hazard ratio [HR], 0.75; 95% CI, 0.61-0.92; nominal P <.005).² The median OS for this combination has not yet been reached. Survival benefits continue to extend beyond the measured follow-up period (not reached [NR]; 95% CI, 42.9-NR). For patients given osimertinib, the median OS was 36.7 months (95% CI, 33.4-41.0), which was consistent with prior studies evaluating osimertinib.

References

1. Popat S, Reckamp KL, Califano R, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA54.

2. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) outperforms osimertinib with a significant and unprecedented overall survival benefit in patients with EGFR-mutated non-small cell lung cancer. News release. Johnson & Johnson. March 26, 2025. Accessed March 26, 2025. https://tinyurl.com/3evwu3cf