MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer

Future Oncol. 2022 Feb;18(6):639-647. doi: 10.2217/fon-2021-0923. Epub 2021 Dec 16.


Third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, have demonstrated efficacy in patients with EGFR-mutant non-small-cell lung cancer; however, almost all patients will eventually relapse. Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations and MET mutations and amplifications. In the ongoing CHRYSALIS study (NCT02609776), amivantamab in combination with lazertinib, a potent, brain-penetrant third-generation EGFR TKI, demonstrated antitumor activity in the treatment-naive and osimertinib-relapsed setting. Here the authors present the methodology for the MARIPOSA study (NCT04487080), a phase 3, multicenter, randomized study designed to compare the efficacy and safety of amivantamab and lazertinib combination therapy versus single-agent osimertinib as first-line treatment for EGFR-mutant non-small-cell lung cancer.

Keywords: EGFR mutations; amivantamab; lazertinib; non-small-cell lung cancer; tyrosine kinase inhibitors.

Plain language summary

Plain language summary Osimertinib is the standard-of-care treatment for patients with non-small-cell lung cancer caused by mutations in the EGFR. However, patients will eventually see their disease return because their tumors will develop new mutations that are resistant to osimertinib treatment. Amivantamab is a new antibody treatment that blocks the EGFR and another receptor called the MET receptor, to stop the growth of lung tumor cells. In an ongoing clinical trial, called the CHRYSALIS study, when amivantamab was given with lazertinib (another drug that blocks the EGFR), lung tumors shrank in patients whose lung cancer had not been previously treated. A new clinical trial called the MARIPOSA study (NCT04487080) aims to compare the antitumor activity and safety of the amivantamab + lazertinib combination versus osimertinib alone in patients with EGFR-mutant non-small-cell lung cancer who have not received treatment for their lung cancer. Trial registration number: NCT04487080 (

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Acrylamides / adverse effects
  • Acrylamides / therapeutic use
  • Adolescent
  • Adult
  • Aniline Compounds / adverse effects
  • Aniline Compounds / therapeutic use
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / therapeutic use
  • Antineoplastic Agents, Immunological* / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Clinical Trials, Phase III as Topic
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Morpholines / adverse effects
  • Morpholines / therapeutic use
  • Multicenter Studies as Topic
  • Mutation
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Research Design
  • Young Adult


  • Acrylamides
  • amivantamab-vmjw
  • Aniline Compounds
  • Antibodies, Bispecific
  • Antineoplastic Agents, Immunological
  • EGFR protein, human
  • ErbB Receptors
  • lazertinib
  • Morpholines
  • osimertinib
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines

Associated data