FDA Approves Lazertinib in Combination with Amivantamab-vmjw as First-Line Treatment for EGFR Exon 19 Deletion or L858R-Mutated Locally Advanced or Metastatic NSCLC

MARIPOSA (NCT04487080) is an international, multicenter, randomized, controlled Phase III clinical trial. A total of 1074 patients with advanced NSCLC who had not received systemic treatment were randomly assigned in a 2:2:1 ratio to receive either lazertinib in combination with amivantamab, osimertinib monotherapy, or lazertinib monotherapy. The primary endpoint of the study is progression-free survival (PFS) assessed by blinded independent central review (BICR).

The results showed that, compared with osimertinib, lazertinib combined with amivantamab demonstrated a statistically significant improvement in PFS, with an HR of 0.70 (95% CI: 0.58, 0.85; p=0.0002). The median PFS was 23.7 months and 16.6 months, respectively.

Although the overall survival (OS) results are not yet mature, no unfavorable trends have been observed for the combination of lazertinib and amivantamab treatment. Additionally, the objective response rates observed in the lazertinib plus amivantamab group and the osimertinib group were 86% and 85%, respectively; the combination therapy showed a longer median duration of response compared to osimertinib (25.8 months vs. 16.8 months).

However, the FDA also pointed out, "A serious safety signal of venous thromboembolic events (VTE) has been observed in patients receiving lazertinib in combination with amivantamab, and prophylactic anticoagulation therapy is recommended during the first four months of treatment."

The results of the MARIPOSA study were first presented at the 2023 ESMO Congress, and the long-term follow-up data from this study will be disclosed at the upcoming 2024 WCLC conference.