https://orcid.org/0000-0002-5562-270X
Abstract
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.
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 (ClinicalTrials.gov)
Financial & competing interests disclosure
The study is funded by Janssen Research & Development LLC. BC Cho research funding: Novartis, Bayer, AstraZeneca, Champions Oncology, Janssen, Yuhan, Ono, MSD, Abbvie, Medpacto, GIInnovation, Eli Lilly, Blueprint, Interpark Bio Convergence Corp., KANAPH Therapeutic, Inc. Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint. Stock ownership: TheraCanVac, Inc., Gencurix, Inc., Bridgebio Therapeutics, KANAPH Therapeutic, Inc., Cyrus Therapeutics Scientific Advisory Board: KANAPH Therapeutic, Inc., Brigebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec, Inc. Board of Directors: Gencurix, Inc., Interpark Bio Convergence Corp. Royalty: Champions Oncology, Founder: DAAN Biotherapeutics. E Felip consulting fees: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Guardant Health, Janssen Biotech, Medscape, Merck KGaA, Merck Sharp and Dohme, Novartis, Pfizer, Prime Oncology, Samsung, Takeda Oncology, Touchtime. Grant/Contract: Fundación Merck Salud, Merck Grant for Oncology Innovation. H Hayashi honoraria: Astra-Zeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co. Ltd, Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD, K.K., Ono Pharmaceutical Co. Ltd, Pfizer Japan, Inc., and Taiho Pharmaceutical Co. Ltd. Research funding: AbbVie, Inc., AC MEDICAL, Inc., Astellas Pharma, Inc., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd, Eisai Co. Ltd, Eli Lilly Japan K.K., EPS Associates Co. Ltd, GlaxoSmithKline K.K., Japan Clinical Research Operations Co. Ltd, Kyowa Hakko Kirin Co. Ltd, Merck Serono Co. Ltd, MSD K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co. Ltd, PAREXEL International Corp., Pfizer Japan, Inc., PPD-SNBL K.K., Quintiles Transnational Japan K.K., Taiho Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, Yakult Honsha Co. Ltd. M Thomas consulting fees: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche AG, Lilly Deutschland, Merck Sharp and Dohme, Novartis, Pfizer, Takeda Oncology. S Lu received research support from AstraZeneca, Hutchison, BMS, Heng Rui Beigene and Roche, Hansoh. Received speaker fees from Astra Zeneca, Roche, Hansoh, Hengrui Therapeutics. An advisor and consultant of Astra Zeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, Yuhan Corporation, PrIME Oncology, Menarini, InventisBio Co. Ltd, Roche. B Besse grants from Biogen, Blueprint Medicines, Celgene, GlaxoSmithKline, Ingnyta, Ipsen, Merck, MSD Oncology, Nektar, Spectrum Pharmaceuticals, Takeda, and Tiziana Therapeutics, outside the submitted work. T Sun, M Martinez, SN Sethi, SM Shreeve are employees of Johnson & Johnson and may hold company stocks. AI Spira personal fees from Array, Mirati, Novartis, Roche, Bluepoint, Merck, CytomX, and AstraZeneca; Janssen, Amgen, Mirati Novartis. Grants from AbbVie, Roche, Novartis, Arch, Mirati, Takeda, and CytomX; nonfinancial support from CytomX. 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.
S Pitre, CMPP™ (SIRO Clinpharm Pvt. Ltd, India) provided writing assistance and T Cao (Janssen Global Services) provided additional editorial support, funded by Janssen Global Services, LLC.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human investigations. Informed consent has been obtained from the participants involved.
Data sharing statement
The data sharing policy of the study sponsor, Janssen Pharmaceutical Companies of Johnson & Johnson, is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) project site at http://yoda.yale.edu
