Plain language summary of MARIPOSA-2: amivantamab-chemotherapy either with or without lazertinib for treatment of non-small-cell lung cancer
- PMID: 40326044
- PMCID: PMC12140441
- DOI: 10.1080/14796694.2025.2492456
Plain language summary of MARIPOSA-2: amivantamab-chemotherapy either with or without lazertinib for treatment of non-small-cell lung cancer
Plain language summary
What is this summary about?This plain language summary describes the first results of the phase 3 MARIPOSA-2 study in patients with locally advanced or metastatic NSCLC with common alterations (exon 19 deletion alteration [Ex19del] or exon 21 L858R substitution alteration [L858R]) in the epidermal growth factor receptor (EGFR) gene whose disease progressed while on or after they received the osimertinib, a third generation tyrosine kinase inhibitor (TKI). Osimertinib, a drug given for NSCLC that helps block the growth and multiplication of cancer cells, is currently a preferred option for patients who have not received prior treatment, as recommended by the National Comprehensive Cancer Network® (NCCN®).Amivantamab in combination with chemotherapy was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR Ex19del or L858R whose disease had progressed on or after treatment with an EGFR TKI. The NCCN recommends amivantamab plus chemotherapy (carboplatin and pemetrexed) as a preferred treatment option for patients with EGFR Ex19del or L858R who have multiple tumors, or lesions, and experience disease progression after receiving first-line osimertinib.What were the results?657 patients were randomly assigned to treatment groups (patients received amivantamab plus chemotherapy, amivantamab plus lazertinib plus chemotherapy, or chemotherapy alone). Patients who received amivantamab plus chemotherapy and amivantamab plus lazertinib plus chemotherapy had their risk of their cancer getting worse or dying reduced by 52% and 56%, respectively, compared with patients who received chemotherapy alone. Similar benefits with amivantamab plus chemotherapy were seen for reducing the risk of cancer growing in the brain. Furthermore, more than 6 in 10 patients who received amivantamab plus chemotherapy or amivantamab plus lazertinib plus chemotherapy had tumors that shrank by at least 30% or were no longer detectable. This only happened in approximately 3 in 10 patients who received chemotherapy alone.Side effects can be seen with all cancer treatments. Most side effects are known and manageable. The most common side effects in patients treated with amivantamab plus chemotherapy and amivantamab plus lazertinib plus chemotherapy were hematologic. Few patients who received amivantamab plus chemotherapy or amivantamab plus lazertinib plus chemotherapy stopped all treatments due to side effects.What do the results mean?In patients with NSCLC with EGFR Ex19del or L858R, amivantamab-containing combinations reduced the risk of a patient’s cancer getting worse or dying. Therefore, they are effective treatment options for patients with NSCLC with EGFR Ex19del or L858R after disease progression on an EGFR TKI.[Box: see text].
Conflict of interest statement
ABC received grants for his institution by Exeliom; received consulting fees from AbbVie, Amgen, AstraZeneca, Exeliom, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol Myers Squibb, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Roche, and Takeda; and received support for attending meetings and/or travel from Amgen, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, and Roche. RDG received grants or contracts from Alliance Foundation, Amgen, AstraZeneca, Big Ten Research Consortium, Bristol Myers Squibb, Chugai, Daiichi Sankyo, ECOG/ACRIN, Helsinn, Hoosier Cancer Research Network, Johnson & Johnson, Jounce Therapeutics, Merck, NCI, Pfizer, SWOG, and Takeda; received honoraria for lectures from Clinical Care Options, OncLive, Society for Immunotherapy of Cancer, and Targeted Oncology; and received support for attending meetings and/or travel from the International Association for the Study of Lung Cancer. KLR received honoraria from Amgen, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Eli Lilly, EMD Serono, Genentech, GSK, Johnson & Johnson, Merck KGA, Mirati, Seattle Genetics, and Takeda; received writing assistance from Blueprint Medicines, Genentech, Johnson & Johnson, Merck, Mirati, Seattle Genetics, and Takeda; and received research funding to her institution from Blueprint Medicines, Calithera, Daiichi Sankyo, Elevation Oncology, Genentech, and Johnson & Johnson. SS is an employee and shareholder of Johnson & Johnson. WNWJr received grants or contracts from AstraZeneca, Bristol Myers Squibb, Johnson & Johnson, Merck, Merck Sharp & Dohme, and Sanofi; received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, and Takeda; received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, and Takeda; received support for attending meetings and/or travel from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Merck, and Sanofi; and owns stock or stock options in Io9. BCC owns stock or stock options in BridgeBio Therapeutics, Cyrus Therapeutics, Gencurix Inc., Interpark Bio Convergence Corp., J INTS BIO, KANAPH Therapeutics, and TheraCanVac; owns royalties, intellectual property, or is a patent beneficiary in Champions Oncology, Crown Bioscience, and Imagen; received research funding from AbbVie, Abion, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio Therapeutics, CHA Bundang Medical Center, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Dong-A ST, Eli Lilly, Genexine, GI-Cell, GI Innovation, Hanmi, Illumina, ImmuneOncia, Interpark Bio Convergence Corp., J INTS BIO, Johnson & Johnson, KANAPH Therapeutics, LG Chem, Merck Sharp & Dohme, MOGAM Institute, Novartis, Nuvalent, Oncternal, Ono, Oscotec, Regeneron, Therapex, and Yuhan; served as a consultant for Abion, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, CJ Bioscience, CureLogen, Cyrus Therapeutics, Eli Lilly, GI-Cell, Guardant, Hanmi, HK Inno-N, Imnewrun Biosciences, Johnson & Johnson, MedPacto, Merck Sharp & Dohme, Novartis, Onegene Biotechnology, Ono, Pfizer, Rand Bioscience, Roche, Takeda, and Yuhan; is the founder of DAAN Biotherapeutics; and is a member of the board of directors for J INTS BIO and Interpark Bio Convergence Corp.
AP serves in a consulting or advisory role for AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo Europe, Johnson & Johnson Innovative Medicine, Merck Sharp & Dohme, Novartis, Pfizer, and Roche/Genentech; and participated in a speakers bureau for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo Europe, Johnson & Johnson, and Merck Sharp & Dohme. ABC participated on a data safety monitoring board or advisory board for InhaTarget and Merck. RDG participated on a data safety monitoring board or advisory board for AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Gilead, Jazz Pharmaceuticals, Johnson & Johnson, Mirati, Oncocyte, Sanofi, and Takeda; is a member of the ASCO Scientific Review Committee and the NCI Investigational Drug Steering Committee; is a co-chair for the Hoosier Cancer Research Network and the Thoracic Clinical Trial Working Group; and is an associate editor for ASCO meeting abstracts and the Journal of Clinical Oncology. WNWJr participated on a data safety monitoring board or advisory board for Io9; and holds an unpaid leadership or fiduciary role in Sociedade Brasileira de Oncologia Clinica and the Latin American Cooperative Oncology Group. BCC participated in an advisory board for BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, KANAPH Therapeutics, and Oscotec.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
The authors acknowledge Claire E. Brady, PharmD, CMPP, of Lumanity Communications Inc., for medical writing support, which was funded by Johnson & Johnson, in accordance with Good Publication Practice 2022 guidelines (
Patient reviewers on this PLSP have received honorarium from
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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