Expert oncologist Alex Spira, MD, PhD, FACP, reviews primary results from the MARIPOSA study in advanced NSCLC following the ESMO 2023 annual meeting.
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