Amivantamab + Lazertinib Versus Osimertinib as 1L Treatment in EGFR-Mutated Advanced NSCLC: Primary Results From MARIPOSA

Amivantamab Plus Lazertinib Versus Osimertinib as First-line Treatment in EGFR-mutated Advanced NSCLC: Primary Results from MARIPOSA, a Phase 3, Global, Randomized, Controlled Trial

Background

• EGFR mutations are present in 15% to 50% of non-squamous advanced NSCLC
• Secondary EGFR or MET alterations may account for 25% to 50% of tumor resistance
• Combining amivantamab, an EGFR-MET bispecific, and lazertinib, an EGFR TKI, may improve clinical outcomes without the addition of chemotherapy

Study Design

• MARIPOSA is phase 3 study combining amivantamab and lazertinib compared to osimertinib as frontline therapy for patients with locally advanced or metastatic NSCLC
  • Patients were treatment-naïve for advanced disease, ECOG PS 0 or 1, and showed documented EGFR Ex19del or L858R
  • Patients were stratified by EGFR mutation type, race, and history of brain metastases
  • Randomization occurred 2:2:1 to amivantamab + lazertinib, osimertinib, or lazertinib
• Primary endpoint was PFS by BICR per RECIST v1.1
• Secondary endpoints included OS, ORR, DoR, PFS2, symptomatic PFS, intracranial PFS, and safety

Results

• Amivantamab + lazertinib reduced the risk of progression or death by 30% and improved median PFS by 7.1 months
• Amivantamab + lazertinib reduced the risk of extracranial progression or death by 32% and improved median PFS by 9 months
• Amivantamab + lazertinib showed consistent PFS benefit with or without brain metastases
• Amivantamab + lazertinib improved median DoR by 9 months, suggesting longer time to resistance and progression
• Amivantamab + lazertinib reduced the risk of 2nd disease progression or death by 25%
• Early survival data show a trend favoring amivantamab + lazertinib vs osimertinib
• Safety profile of amivantamab + lazertinib was consistent with prior reports (higher rates of EGFR- and MET-related AEs and VTEs, majority grade 1-2)
• Amivantamab + lazertinib represents a new standard of care in patients with first-line, EGFR-mutant advanced NSCLC