Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study

Introduction: Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant 3^rd-generation EGFR TKI. In the primary analysis of the phase 3 MARIPOSA study (NCT04487080), at a median follow-up of 22.0 months, ami plus laz significantly improved progression-free survival (PFS) by blinded independent central review vs osimertinib (osi) in patients with treatment-naïve, EGFR-mutated advanced NSCLC (HR, 0.70; 95% CI, 0.58-0.85; P<0.001). Early interim overall survival (OS) analysis showed a favorable trend for ami-laz over osi (HR, 0.80; 95% CI, 0.61-1.05; P=0.11). Here, we present updated results with longer follow-up from MARIPOSA.

Methods: MARIPOSA randomized 1074 patients with treatment-naïve, EGFR-mutated (Exon 19 del or Exon 21 L858R substitutions) locally advanced or metastatic NSCLC 2:2:1 to open-label ami-laz (n=429), blinded osi (n=429), or blinded laz (n=216). This analysis, requested by health authorities, compares ami-laz with osi.

Results: At a median follow-upof 31.1 months, 44% (185/421) and 34% (145/428) of patients were still on treatment in the ami-laz and osi arms, respectively. In total, 155 patients in the ami-laz arm and 233 in the osi arm had investigator-assessed progressive disease and discontinued treatment. Of those, 72% (111/155) and 74% (173/233) initiated subsequent therapy, respectively, with carbo-pem being the most common first subsequent therapy across arms (ami-laz, 26% [29/111]; osi, 28% [48/173]). PFS after first subsequent therapy (PFS2) favored ami-laz (HR, 0.73; 95% CI, 0.59-0.91; nominal P=0.004). Patients receiving ami-laz demonstrated significantly longer median time to treatment discontinuation and time to subsequent therapy vs osi. Intracranial PFS showed a favorable trend for ami-laz vs osi . While not formally tested for significance, median OS was not estimable for ami-laz vs 37.3 months for osi (HR, 0.77; 95% CI, 0.61-0.96; nominal P=0.019). At 24 months, 75% and 70% of patients were alive in the ami-laz and osi arms, respectively; corresponding values at 36 months were 61% and 53%.

Conclusions: Ami-laz continues to show a trend towards improved OS while also improving post-progression outcomes vs osi, reaffirming ami-laz as a first-line standard-of-care for EGFR-mutated advanced NSCLC.

Publication History

Article published online:
18 March 2025