Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study
Bibliographic record
Abstract
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 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.006 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".