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Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study

Krebs, M. G.
; 
Cho, B. C.
; 
Hiret, S.
; 
Han, J. Y.
; 
Lee, K. H.
; 
Pérez, C. L.
; 
De Braud, F.
; 
Haura, E. B.
; 
Sanborn, R. E.
; 
Chih-Hsin Yang, J.
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Abstract
INTRODUCTION: Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity. We assessed the safety and efficacy of amivantamab in participants with advanced NSCLC harboring primary MET exon 14 skipping mutations (METex14). METHODS: CHRYSALIS enrolled participants with METex14 NSCLC who progressed after or declined standard-of-care therapy. Participants received intravenous amivantamab weekly for 4 weeks and biweekly thereafter. Objective response rate, duration of response (DoR), clinical benefit rate, progression-free survival, overall survival, safety, and circulating tumor DNA were analyzed. RESULTS: Among 97 participants, 16 were treatment naive, 28 received prior treatment without MET therapies, and 53 received prior MET therapies. Objective response rate was 32% overall, 50% in treatment-naive participants, 46% in participants without prior MET therapies, and 19% in participants with prior MET therapies. In participants without prior MET therapies, amivantamab activity was observed regardless of co-occurring genomic alterations. Clinical benefit rate was 69% overall, 88% in treatment-naive participants, 64% in participants without prior MET therapies, and 66% in participants with prior MET therapies. Median DoR was 11.2 months; 61% (19/31) of the responders had DoR greater than or equal to 6 months. Median progression-free survival was 5.3 months (95% confidence interval, 4.3-7.0); median overall survival was 15.8 months (95% confidence interval, 14.6-not estimable). Most common adverse events were rash (79%) and infusion-related reactions (72%), most being grades 1 to 2 (52%). CONCLUSIONS: The safety profile was consistent with previous reports of amivantamab in EGFR-mutant NSCLC. Amivantamab demonstrated clinically meaningful and durable antitumor activity in participants with METex14 advanced NSCLC, including those who progressed on prior MET therapies.
Authors
Krebs, M. G.
Cho, B. C.
Hiret, S.
Han, J. Y.
Lee, K. H.
Pérez, C. L.
De Braud, F.
Haura, E. B.
Sanborn, R. E.
Chih-Hsin Yang, J.
Shu, C. A.
Goto, K.
Nishio, M.
Zhao, J.
Wang, Z.
Tomasini, P.
Felip, E.
Goldman, J. W.
Ignatius Ou, S. H.
Boyer, M.
Gao, G.
Qu, S.
Curtin, J. C.
Lyu, X.
Schnepp, R. W.
Kim, P.
Thayu, M.
Knoblauch, R. E.
Lorenzini, P.
Baig, M.
Spira, A. I.
Leighl, N. B.
Affiliation
Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom. Electronic address: matthew.krebs@nhs.net. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Medical Oncology Department, Institut de Cancérologie de l'Ouest, Saint-Herblain, France. National Cancer Center, Goyang-si, Republic of Korea. Chungbuk National University Hospital, Cheongju, Republic of Korea. Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIsnowMA, Málaga, Spain. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. National Taiwan University Cancer Center, Taipei, Taiwan. Columbia University Medical Center, New York, New York. National Cancer Center Hospital East, Kashiwa, Japan. Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hopital de La Timone, Marseille, France. Medical Oncology Service, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. University of California Irvine School of Medicine, Orange, California. Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. Johnson & Johnson, Shanghai, People's Republic of China. Johnson & Johnson, Spring House, Pennsylvania. Johnson & Johnson, Raritan, New Jersey. Virginia Cancer Specialists, Fairfax, Virginia. Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
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2025
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All Christie Publications
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Article
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Krebs MG, Cho BC, Hiret S, Han JY, Lee KH, Pérez CL, et al. Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2025 Sep;20(9):1289-301. PubMed PMID: 40383434. Epub 2025/05/19. eng.
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https://christie.openrepository.com/handle/10541/627492
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