Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.

Byoung C. Cho; Shun Lu; Enriqueta Felip; Alexander I. Spira; Nicolas Girard; Jong Seok Lee; Se Hoon Lee; Yurii Ostapenko; Pongwut Danchaivijitr; Baogang Liu; Adlinda Alip; Ernesto Korbenfeld; Josiane Mourão Dias; Benjamin Besse; Ki Hyeong Lee; Hailin Xiong; Soon Hin How; Ying Cheng; Gee Chen Chang; Hiroshige Yoshioka; James C.H. Yang; Michael Thomas; Danny Nguyen; Sai Hong I. Ou; Sanjay Mukhedkar; Kumar Prabhash; Manolo D'Arcangelo; Jorge Alatorre-Alexander; Juan C. Vázquez Limón; Sara Alves; Daniil Stroyakovskiy; Marina Peregudova; Mehmet A.N. Şendur; Ozan Yazici; Raffaele Califano; Vanesa Gutiérrez Calderón; Filippo De Marinis; Antonio Passaro; Sang We Kim; Shirish M. Gadgeel; John Xie; Tao Sun; Melissa Martinez; Mariah Ennis; Elizabeth Fennema; Mahesh Daksh; Dawn Millington; Isabelle Leconte; Ryota Iwasawa; Patricia Lorenzini; Mahadi Baig; Sujay Shah; Joshua M. Bauml; S. Martin Shreeve; Seema Sethi; Roland E. Knoblauch; Hidetoshi Hayashi

doi:10.1056/NEJMoa2403614

Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.

Byoung C. Cho
, Shun Lu
, Enriqueta Felip
, Alexander I. Spira
, Nicolas Girard
, Jong Seok Lee
, Se Hoon Lee
, Yurii Ostapenko
, Pongwut Danchaivijitr
, Baogang Liu
, Adlinda Alip
, Ernesto Korbenfeld
, Josiane Mourão Dias
, Benjamin Besse
, Ki Hyeong Lee
, Hailin Xiong
, Soon Hin How
, Ying Cheng
, Gee Chen Chang
, Hiroshige Yoshioka

James C.H. Yang, Michael Thomas, Danny Nguyen, Sai Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D'Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo De Marinis, Antonio Passaro, Sang We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, Hidetoshi Hayashi

Department of Medicine

Yonsei University College of Medicine
Shanghai Chest Hospital
University Hospital Vall d'Hebron
Virginia Cancer Specialists
Institut Curie
Université Versailles-Saint-Quentin
Seoul National University Bundang Hospital
Samsung Medical Center, Sungkyunkwan university
National Cancer Institute of Ukraine
The Fourth Affiliated Hospital of Harbin Medical University
University of Malaya
British Hospital of Buenos Aires - Central British Hospital
Barretos Cancer Hospital
Université Paris-Sud
Chungbuk National University Hospital
Huizhou Municipal Central Hospital of Guangdong Province
International Islamic University Malaysia
Jilin Provincial Hospital
Chung Shan Medical University
Chung Shan Medical University Hospital
Kansai Medical University Hospital
National Taiwan University Hospital
Thoraxklinik at the University Hospital Heidelberg
Comprehensive Cancer Center
University of California
St. John of God Murdoch Hospital
Homi Bhabha National Institute
Santa Maria delle Croci Hospital
Health Pharma Professional Research S.A de C.V.
University of Guadalajara Health Sciences Centre
Instituto Português de Oncologia Do Porto
Moscow City Oncology Hospital No. 62
Medical Center in Kolomenskoe
Ankara Yildirim Beyazit University
Gazi University, Faculty of Medicine
Faculty of Biology, Medicine and Health
Hosp Carlos Haya
IRCCS
Asan Medical Center
Henry Ford Health
Janssen Research and Development
Johnson & Johnson
Kinki University School of Medicine

Research output: Contribution to journal › Article › peer-review

359 Citations (Scopus)

Abstract

Background Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). Methods In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Results Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Conclusions Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

Original language	English
Pages (from-to)	1486-1498
Number of pages	13
Journal	New England Journal of Medicine
Volume	391
Issue number	16
DOIs	https://doi.org/10.1056/NEJMoa2403614
Publication status	Published - 24 Oct 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hematology/Oncology
Lung Cancer
Pulmonary/Critical Care
Pulmonary/Critical Care General
Treatments in Oncology

Access to Document

10.1056/NEJMoa2403614

Cite this

Cho, B. C., Lu, S., Felip, E., Spira, A. I., Girard, N., Lee, J. S., Lee, S. H., Ostapenko, Y., Danchaivijitr, P., Liu, B., Alip, A., Korbenfeld, E., Mourão Dias, J., Besse, B., Lee, K. H., Xiong, H., How, S. H., Cheng, Y., Chang, G. C., ... Hayashi, H. (2024). Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC. New England Journal of Medicine, 391(16), 1486-1498. https://doi.org/10.1056/NEJMoa2403614

@article{6e69dbc37c4c47f68830deb4b87a65d6,

title = "Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.",

abstract = "Background Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). Methods In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Results Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95\% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86\% of the patients (95\% CI, 83 to 89) in the amivantamab-lazertinib group and in 85\% of those (95\% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95\% CI, 20.1 to could not be estimated) and 16.8 months (95\% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95\% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10\% with amivantamab-lazertinib and 3\% with osimertinib. Conclusions Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)",

keywords = "Hematology/Oncology, Lung Cancer, Pulmonary/Critical Care, Pulmonary/Critical Care General, Treatments in Oncology",

author = "Cho, \{Byoung C.\} and Shun Lu and Enriqueta Felip and Spira, \{Alexander I.\} and Nicolas Girard and Lee, \{Jong Seok\} and Lee, \{Se Hoon\} and Yurii Ostapenko and Pongwut Danchaivijitr and Baogang Liu and Adlinda Alip and Ernesto Korbenfeld and \{Mour{\~a}o Dias\}, Josiane and Benjamin Besse and Lee, \{Ki Hyeong\} and Hailin Xiong and How, \{Soon Hin\} and Ying Cheng and Chang, \{Gee Chen\} and Hiroshige Yoshioka and Yang, \{James C.H.\} and Michael Thomas and Danny Nguyen and Ou, \{Sai Hong I.\} and Sanjay Mukhedkar and Kumar Prabhash and Manolo D'Arcangelo and Jorge Alatorre-Alexander and \{V{\'a}zquez Lim{\'o}n\}, \{Juan C.\} and Sara Alves and Daniil Stroyakovskiy and Marina Peregudova and {\c S}endur, \{Mehmet A.N.\} and Ozan Yazici and Raffaele Califano and \{Guti{\'e}rrez Calder{\'o}n\}, Vanesa and \{De Marinis\}, Filippo and Antonio Passaro and Kim, \{Sang We\} and Gadgeel, \{Shirish M.\} and John Xie and Tao Sun and Melissa Martinez and Mariah Ennis and Elizabeth Fennema and Mahesh Daksh and Dawn Millington and Isabelle Leconte and Ryota Iwasawa and Patricia Lorenzini and Mahadi Baig and Sujay Shah and Bauml, \{Joshua M.\} and Shreeve, \{S. Martin\} and Seema Sethi and Knoblauch, \{Roland E.\} and Hidetoshi Hayashi",

note = "Publisher Copyright: {\textcopyright} 2024 Massachusetts Medical Society.",

year = "2024",

month = oct,

day = "24",

doi = "10.1056/NEJMoa2403614",

language = "English",

volume = "391",

pages = "1486--1498",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "16",

}

Cho, BC, Lu, S, Felip, E, Spira, AI, Girard, N, Lee, JS, Lee, SH, Ostapenko, Y, Danchaivijitr, P, Liu, B, Alip, A, Korbenfeld, E, Mourão Dias, J, Besse, B, Lee, KH, Xiong, H, How, SH, Cheng, Y, Chang, GC, Yoshioka, H, Yang, JCH, Thomas, M, Nguyen, D, Ou, SHI, Mukhedkar, S, Prabhash, K, D'Arcangelo, M, Alatorre-Alexander, J, Vázquez Limón, JC, Alves, S, Stroyakovskiy, D, Peregudova, M, Şendur, MAN, Yazici, O, Califano, R, Gutiérrez Calderón, V, De Marinis, F, Passaro, A, Kim, SW, Gadgeel, SM, Xie, J, Sun, T, Martinez, M, Ennis, M, Fennema, E, Daksh, M, Millington, D, Leconte, I, Iwasawa, R, Lorenzini, P, Baig, M, Shah, S, Bauml, JM, Shreeve, SM, Sethi, S, Knoblauch, RE & Hayashi, H 2024, 'Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.', New England Journal of Medicine, vol. 391, no. 16, pp. 1486-1498. https://doi.org/10.1056/NEJMoa2403614

TY - JOUR

T1 - Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.

AU - Cho, Byoung C.

AU - Lu, Shun

AU - Felip, Enriqueta

AU - Spira, Alexander I.

AU - Girard, Nicolas

AU - Lee, Jong Seok

AU - Lee, Se Hoon

AU - Ostapenko, Yurii

AU - Danchaivijitr, Pongwut

AU - Liu, Baogang

AU - Alip, Adlinda

AU - Korbenfeld, Ernesto

AU - Mourão Dias, Josiane

AU - Besse, Benjamin

AU - Lee, Ki Hyeong

AU - Xiong, Hailin

AU - How, Soon Hin

AU - Cheng, Ying

AU - Chang, Gee Chen

AU - Yoshioka, Hiroshige

AU - Yang, James C.H.

AU - Thomas, Michael

AU - Nguyen, Danny

AU - Ou, Sai Hong I.

AU - Mukhedkar, Sanjay

AU - Prabhash, Kumar

AU - D'Arcangelo, Manolo

AU - Alatorre-Alexander, Jorge

AU - Vázquez Limón, Juan C.

AU - Alves, Sara

AU - Stroyakovskiy, Daniil

AU - Peregudova, Marina

AU - Şendur, Mehmet A.N.

AU - Yazici, Ozan

AU - Califano, Raffaele

AU - Gutiérrez Calderón, Vanesa

AU - De Marinis, Filippo

AU - Passaro, Antonio

AU - Kim, Sang We

AU - Gadgeel, Shirish M.

AU - Xie, John

AU - Sun, Tao

AU - Martinez, Melissa

AU - Ennis, Mariah

AU - Fennema, Elizabeth

AU - Daksh, Mahesh

AU - Millington, Dawn

AU - Leconte, Isabelle

AU - Iwasawa, Ryota

AU - Lorenzini, Patricia

AU - Baig, Mahadi

AU - Shah, Sujay

AU - Bauml, Joshua M.

AU - Shreeve, S. Martin

AU - Sethi, Seema

AU - Knoblauch, Roland E.

AU - Hayashi, Hidetoshi

PY - 2024/10/24

Y1 - 2024/10/24

N2 - Background Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). Methods In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Results Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Conclusions Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

AB - Background Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). Methods In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Results Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Conclusions Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)

KW - Hematology/Oncology

KW - Lung Cancer

KW - Pulmonary/Critical Care

KW - Pulmonary/Critical Care General

KW - Treatments in Oncology

UR - https://www.scopus.com/pages/publications/85199638052

U2 - 10.1056/NEJMoa2403614

DO - 10.1056/NEJMoa2403614

M3 - Article

C2 - 38924756

AN - SCOPUS:85199638052

SN - 0028-4793

VL - 391

SP - 1486

EP - 1498

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 16

ER -

Amivantamab plus Lazertinib in Previously Untreated EGFR -Mutated Advanced NSCLC.

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