# Amivantamab + lazertinib (first-line EGFR NSCLC)

Source: https://onco.cc/pairings/amivantamab-plus-lazertinib/  
OnCo record `amivantamab-plus-lazertinib` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Blocking EGFR from inside (a pill) and outside (an antibody that also blocks MET) beat osimertinib and added more than a year of survival.

## Summary

This combination pairs amivantamab, a bispecific antibody against EGFR and MET, with lazertinib, an oral EGFR inhibitor, as first-line treatment for EGFR-mutant non-small-cell lung cancer. Lazertinib blocks EGFR signalling from inside the cell while amivantamab blocks EGFR and MET at the cell surface and recruits immune effectors, so the pairing pre-empts the two main escape routes from osimertinib, MET amplification and the C797S mutation. The phase 3 MARIPOSA trial compared it with osimertinib and showed a progression-free and overall survival benefit. The price is more toxicity, including rash, paronychia, venous thromboembolism and infusion reactions, plus intravenous visits; subcutaneous amivantamab, introduced in 2025, eases the latter.

## Fields

- Kind: Pairing
- Last checked: 2026-09-06
- Pairs: Amivantamab + Lazertinib
- Type: combination
- Rationale: Lazertinib blocks intracellular EGFR signalling while amivantamab blocks EGFR and MET extracellularly and recruits immune effectors, pre-empting the MET-amplification and C797S escape routes.
- Evidence: Phase 3 with OS benefit.

## Sources

- ClinicalTrials.gov NCT04487080: MARIPOSA: https://clinicaltrials.gov/study/NCT04487080

## Connected records

- cancers: [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- 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/)
- terms: [EGFR C797S](https://onco.cc/terms/c797s/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/)
- trials: [MARIPOSA](https://onco.cc/trials/mariposa/)

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