# Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC

Source: https://onco.cc/key-papers/paper-cho-mariposa-amivantamab-lazertinib-nejm-2024/  
OnCo record `paper-cho-mariposa-amivantamab-lazertinib-nejm-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MARIPOSA beat osimertinib, the standard first treatment, by about seven months before the cancer grew again. It is the first trial to do so, and the first to show that hitting EGFR two ways at once is better than one.

## Summary

The MARIPOSA investigators, reported by Cho, Lu, Felip and colleagues, randomised 1,074 patients with previously untreated EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic non-small-cell lung cancer 2 to 2 to 1 between amivantamab with lazertinib (open-label), osimertinib (blinded) and lazertinib alone (blinded, to assess the contribution of each component). The primary endpoint was blinded independent central review progression-free survival against osimertinib.

The third arm is the methodological point: a combination trial that can say whether the combination is better than either of its parts, rather than only better than the comparator. The cost is toxicity, and the discontinuation figures are the argument against giving it to everybody.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/NEJMoa2403614
- Authors: Cho BC, Lu S, Felip E, et al.
- Findings: Median progression-free survival 23.7 months with amivantamab and lazertinib against 16.6 months with osimertinib: hazard ratio for progression or death 0.70 (95 percent confidence interval 0.58 to 0.85).; 1,074 patients were randomised: 429 to amivantamab and lazertinib, 429 to osimertinib and 216 to lazertinib alone.; Discontinuation of all agents because of treatment-related adverse events occurred in 10 percent with amivantamab and lazertinib against 3 percent with osimertinib.
- What it means: The first regimen to beat osimertinib as first-line treatment for EGFR-mutant lung cancer. It sets up the choice that now faces every newly diagnosed patient: a more effective but harder combination now, or a simpler tablet with something held back for later.
- Caveats: Open-label combination arm against blinded comparators; investigator and patient knowledge can influence progression assessment even under central review.; Substantially more infusion-related and skin toxicity, and a threefold higher rate of stopping all treatment for adverse events.; Overall survival, and how it compares with FLAURA2's chemotherapy combination, was not mature at this report.

## Sources

- N Engl J Med 2024: https://doi.org/10.1056/NEJMoa2403614
- PubMed: https://pubmed.ncbi.nlm.nih.gov/38924756/
- ClinicalTrials.gov NCT04487080: https://clinicaltrials.gov/study/NCT04487080

## Connected records

- key papers: [Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer](https://onco.cc/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/), [FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-flaura-nejm-2018/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC](https://onco.cc/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/)
- cancers: [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [MET](https://onco.cc/targets/met/)
- drugs: [Amivantamab](https://onco.cc/drugs/amivantamab/), [Lazertinib](https://onco.cc/drugs/lazertinib/), [Osimertinib](https://onco.cc/drugs/osimertinib/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- trials: [MARIPOSA](https://onco.cc/trials/mariposa/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- ideas: [Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became](https://onco.cc/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/)

---
JSON: https://onco.cc/api/v1/entities/paper-cho-mariposa-amivantamab-lazertinib-nejm-2024.json