FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer
Regulatory approval: On Aug 19, 2024, the FDA approved lazertinib (Lazcluze) plus amivantamab-vmjw (Rybrevant) for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations detected by an FDA-approved test. Approval was supported by MARIPOSA (NCT04487080), where the combination improved BICR-assessed PFS versus osimertinib (HR 0.70; median 23.7 vs 16.6 months). OS data were immature.
FDA approval (Aug 19, 2024): lazertinib + amivantamab-vmjw in EGFR-mutated NSCLC
The FDA approved lazertinib (Lazcluze) in combination with amivantamab-vmjw (Rybrevant) for first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
Supporting evidence: MARIPOSA (NCT04487080)
MARIPOSA was a randomized, active-controlled, multicenter trial (n=1074) enrolling patients with EGFR exon 19 deletion or exon 21 L858R mutation–positive locally advanced/metastatic NSCLC and no prior systemic therapy for advanced disease. Patients were randomized (2:2:1) to lazertinib + amivantamab, osimertinib, or lazertinib monotherapy (noted as an unapproved regimen for NSCLC).
- Primary endpoint: PFS by blinded independent central review (BICR) comparing combination vs osimertinib
- PFS: HR 0.70 (95% CI, 0.58–0.85; p=0.0002); median 23.7 vs 16.6 months
- OS: immature (55% of prespecified deaths); no trend toward detriment observed at current analysis
Safety highlights
Common adverse reactions (≥20%) included rash, nail toxicity, infusion-related reactions, VTE, and others. A serious safety signal of venous thromboembolic events was observed; FDA labeling states prophylactic anticoagulation should be administered for the first 4 months.
The review was conducted under Project Orbis and received priority review.