FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations
Regulatory approval: On Sept 19, 2024, the FDA approved amivantamab-vmjw (Rybrevant) with carboplatin and pemetrexed for adults with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations whose disease progressed on or after an EGFR TKI. Approval was supported by the phase 3 MARIPOSA-2 trial, which showed improved BICR-assessed PFS and ORR versus carboplatin/pemetrexed; interim OS was not statistically significant.
FDA approval (Sept 19, 2024)
The FDA approved amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or EGFR exon 21 L858R substitution mutations whose disease has progressed on or after an EGFR tyrosine kinase inhibitor.
Evidence base: MARIPOSA-2 (NCT04988295)
Approval was based on MARIPOSA-2, a randomized, open-label, multicenter trial in 657 patients with locally advanced/metastatic EGFR-mutated NSCLC with progression on or after osimertinib. Patients were randomized (1:2:2) to amivantamab + carboplatin/pemetrexed (amivantamab + CP), carboplatin/pemetrexed (CP), or amivantamab as part of another combination regimen.
- Primary endpoint (PFS by BICR; amivantamab + CP vs CP): median PFS 6.3 vs 4.2 months (HR 0.48, 95% CI 0.36–0.64; p<0.0001)
- Confirmed ORR (BICR): 53% vs 29% (p<0.0001)
- OS: at a prespecified second interim analysis (85% of deaths for final), no statistically significant OS difference; OS HR 0.73 (95% CI 0.54–0.99)
Safety and dosing
Most common adverse reactions (≥20%) included rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection. Dosing is baseline body weight–based.
Regulatory notes
The review was conducted under Project Orbis; reviews remain ongoing at collaborating agencies.