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Clinical Trial
. 2025 Sep;20(9):1289-1301.
doi: 10.1016/j.jtho.2025.05.012. Epub 2025 May 16.

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

Matthew G Krebs  1 , Byoung Chul Cho  2 , Sandrine Hiret  3 , Ji-Youn Han  4 , Ki Hyeong Lee  5 , Casilda Llácer Pérez  6 , Filippo De Braud  7 , Eric B Haura  8 , Rachel E Sanborn  9 , James Chih-Hsin Yang  10 , Catherine A Shu  11 , Koichi Goto  12 , Makoto Nishio  13 , Jun Zhao  14 , Zhijie Wang  15 , Pascale Tomasini  16 , Enriqueta Felip  17 , Jonathan W Goldman  18 , Sai-Hong Ignatius Ou  19 , Michael Boyer  20 , Grace Gao  21 , Siyang Qu  22 , Joshua C Curtin  23 , Xuesong Lyu  21 , Robert W Schnepp  22 , Priya Kim  22 , Meena Thayu  22 , Roland E Knoblauch  22 , Patricia Lorenzini  22 , Mahadi Baig  23 , Alexander I Spira  24 , Natasha B Leighl  25
Affiliations
Free article
Clinical Trial

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

Matthew G Krebs et al. J Thorac Oncol. 2025 Sep.
Free article

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.

Keywords: Advanced non–small cell lung cancer; Amivantamab; CHRYSALIS; MET exon 14 skipping mutation; Previous MET therapies.

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Conflict of interest statement

Disclosure Dr. Krebs served in a consulting or advisory role for Bayer, Guardant Health, Janssen, Roche, Seattle Genetics, and Zai Lab; received travel, accommodations, or expenses from BerGenBio, Janssen, Roche, and Zai Lab; and received grants or contracts from BerGenBio, Novartis, and Roche. Dr. Cho served in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Pfizer, Yuhan Corporation, Janssen, Takeda, Merck Sharp & Dohme, Ono Pharmaceutical, Lilly, MedPacto, Blueprint Medicines, Cyrus Therapeutics, Guardant Health, Novartis, CJ Bioscience, Abion, BeiGene, CureLogen, Onegene Biotechnology, GI Cell, HK inno.N, Imnewrun Biosciences Inc., RandBio, Hanmi, Kanaph Therapeutics, BridgeBio, and Oscotec; served in leadership roles for Interpark Bio and J INTS BIO; holds patents, royalties, or other intellectual property for Champions Oncology, Crown Bioscience, and Imagen; has other relationships with DAAN Biotherapeutics; owns stock or has other ownership interests with Theravance, Gencurix, BridgeBio, Kanaph Therapeutics, Cyrus Therapeutics, Interpark Bio, and J INTS BIO; and received research funding from Novartis, Bayer, AstraZeneca, MOGAM Biotechnology Research Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan Corporation, Ono Pharmaceutical, Dizal Pharma, Merck Sharp & Dohme, AbbVie, GI Innovation, Lilly, Blueprint Medicines, Interpark Bio, LG Chem, Oscotec, GI Cell, Abion, Boehringer Ingelheim, CJ Bioscience, CJ Blossom Park, Cyrus Therapeutics, Genexine, Nuvalent Inc., Oncternal Therapeutics, Regeneron, BridgeBio, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, J INTS BIO, Hanmi, and CHA Bundang Medical Center. Dr. Hiret served in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Roche, Sanofi, and Takeda; and received travel, accommodations, or expenses from Novartis, Merck Sharp & Dohme, and Roche. Dr. Han received grants or contracts from Pfizer, Takeda, Ono Pharmaceutical, and Roche; received consulting fees from AstraZeneca, Janssen, Amgen, Oncobix, Daiichi Sankyo, Merck, Novartis, Abion, and Takeda; received payment or honoraria from AstraZeneca, Janssen, Merck, Novartis, Takeda, Yuhan Corporation, and Pfizer; received payment for expert testimony from AstraZeneca; participated on a data safety monitoring board or advisory board for AstraZeneca and Janssen; and served in a leadership or fiduciary role for National Cancer Drug Assessment Committee. Dr. Lee served in a consulting or advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Lilly; and received research funding from Merck. Dr. Pérez received travel, accommodations, or expenses from Servier, AstraZeneca, and Bristol Myers Squibb. Dr. De Braud served on a speakers bureau for Nadirex, Dephaforum, Ambrosetti, Incyte, Bristol Myers Squibb, Motore Sanità, Fare Comunicazione, Itanet, and ESO; served on an advisory board for Sanofi, Bristol Myers Squibb, Taiho Pharmaceutical, and Incyte; and served in a consulting role for Pierre Fabre, Mattioli 1885, McCann Health, Merck Sharp & Dohme, and IQVIA. Dr. Haura received research funding from Revolution Medicines; served on an advisory board for Revolution Medicines and Janssen; and served in a consulting role for Ellipses, Kanaph Therapeutics, Grove Biotherapeutics, and ORI Capital II, Inc. Dr. Sanborn served on an advisory board for AbbVie, Amgen, AstraZeneca, EMD Serono, Daiichi Sankyo, Inhibrx, Lilly Oncology, Janssen, GE HealthCare, Gilead, IDEOlogy Health, Sanofi, Regeneron, GSK, and G1 Therapeutics; served as an invited speaker for Illumina and PRIME Education; received honoraria for Curio Science and OncLive; participated as a steering committee member for AstraZeneca, BeiGene, GSK, and Johnson & Johnson; received funding from Merck and AstraZeneca; and has other relationships with Bristol Myers Squibb and Jounce Therapeutics. Dr. Yang received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, and Takeda; served in a consulting or advisory role for AbbVie, Amgen, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, GSK, Hansoh, Incyte, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme Oncology, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and Yuhan Corporation; and received travel, accommodations, or expenses from Pfizer. Dr. Shu served on an advisory board for AstraZeneca, Janssen, Gilead, and Genentech; and received honoraria from Curio Science, OncLive, Plexus, MJH Life Sciences, and HMP Global. Dr. Goto received research funding from Amgen, Astellas BioPharma, AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Bristol Myers Squibb, Blueprint Medicines, Chugai Pharmaceutical, Craif, Daiichi Sankyo, Eisai, Lilly Japan, Haihe Biopharma, Ignyta, Janssen, Kissei Pharmaceutical, Kyowa Kirin, Life Technologies Japan, Loxo Oncology, LSI Medience Corporation, Medical & Biological Laboratories, Merck, Merus, Novartis, Ono Pharmaceutical, Pfizer Japan, Riken Genesis, Sysmex, Taiho Pharmaceutical, Takeda, and Turning Point Therapeutics; served on a speakers bureau for Amgen, Amoy Diagnostics, AstraZeneca, Bayer U.S., Boehringer Ingelheim Japan, Bristol Myers Squibb, Lilly Japan, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Guardant Health, Janssen, Life Technologies Japan, Thermo Fisher Scientific, Syneos Health Clinical, Merck, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Riken Genesis, Taiho Pharmaceutical, and Takeda; and served on an advisory board for Amgen, Daiichi Sankyo, and Takeda. Dr. Nishio served on a speakers bureau for Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, Merck Sharp & Dohme, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, and Janssen. Dr. Tomasini received payment or honoraria from AstraZeneca, Takeda, Bristol Myers Squibb, Roche, Janssen, and Amgen; and received support for attending meetings and/or travel from Takeda, AstraZeneca, and Bristol Myers Squibb. Dr. Felip served in a consulting or advisory role for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point Therapeutics, and Daiichi Sankyo; served on a speakers bureau for Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Lilly, Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, PeerVoice, Pfizer, Sanofi, Takeda, and touchONCOLOGY; and received travel, accommodations, or expenses from AstraZeneca, Janssen, and Roche; and has other relationships with Grifols, Hospital Universitari Parc Tauli (Scientific Advisory Committee), Sociedad Española de Oncología Médica (President), and ETOP IBCSG Partners (Scientific Committee). Dr. Goldman served as an invited speaker for AstraZeneca; served on an advisory board for Genentech, Lilly, Janssen, AbbVie, and Gritstone bio; and served as coordinating or local principal investigator for AstraZeneca, Genentech, Janssen, Bristol Myers Squibb, and AbbVie. Dr. Ou served in a consulting or advisory role for Pfizer, Janssen, Daiichi Sankyo, Avistone, Merus, Bristol Myers Squibb, and AnHeart Therapeutics/Nuvation Bio; owns stock or has other ownership interests with Turning Point Therapeutics, Elevation Oncology, MBrace Therapeutics, BlossomHill Therapeutics, Lilly, Nuvalent Inc., and Nuvation Bio; received honoraria from Pfizer, Janssen, DAVA Oncology LLP, OncLive, and Caris Life Sciences; served on an advisory board for Elevation Oncology, Daiichi Sankyo, and AnHeart Therapeutics; and received research funding from Pfizer, Roche, Revolution Medicines, Mirati Therapeutics, Janssen, Nuvalent Inc., Merus, Daiichi Sankyo, Erasca, Merck, Blueprint Medicines, and Takeda. Dr. Boyer received grants or contracts from Amgen, Daiichi Sankyo, Merck Sharp & Dohme, Lilly, Bristol Myers Squibb, AstraZeneca, Roche, Pfizer, Imugene, and Dizal Pharma; received consulting fees from Amgen, AstraZeneca, and Merck Sharp & Dohme; received payment or honoraria from Merck Sharp & Dohme; and served in a leadership or fiduciary role for Thoracic Oncology Group of Australasia. Dr. Gao, Ms. Qu, Dr. Curtin, Dr. Lyu, Dr. Schnepp, Dr. Kim, Dr. Thayu, Dr. Knoblauch, Ms. Lorenzini, and Dr. Baig are employees of and may hold stock in Johnson & Johnson. Dr. Spira served in a consulting or advisory role for Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune, Mirati Therapeutics, Gritstone bio, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb, Takeda, Janssen, Mersana, Blueprint Medicines, Daiichi Sankyo, Regeneron, Lilly, Black Diamond Therapeutics, and Sanofi; served in leadership roles for NEXT Oncology; owns stock or has other ownership interests with Lilly; received honoraria from CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Bayer; and received research funding from Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Incyte, AbbVie, Ignyta, Takeda, MacroGenics, CytomX Therapeutics, LAM Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo Oncology, Arch Therapeutics, Gritstone bio, Plexxikon, Amgen, Daiichi Sankyo, ADC Therapeutics, Janssen, Mirati Therapeutics, Rubius Therapeutics, Synthekine, Mersana, Blueprint Medicines, Regeneron, Alkermes, Revolution Medicines, Medikine, Black Diamond Therapeutics, BluPrint Oncology, Nalo Therapeutics, Scorpion Therapeutics, and ArriVent BioPharma. Dr. Leighl received unrelated grants or contracts from AstraZeneca, GSK, Lilly, Janssen, Merck Sharp & Dohme, NeoGenomics, Novartis, Pfizer, and Takeda; received payment or honoraria for CME lectures from BeiGene, Bristol Myers Squibb, Janssen, Merck, Novartis, and Takeda; received support for meeting travel (CME lectures) from AstraZeneca, Eisai, Guardant Health, Janssen, Merck Sharp & Dohme, Roche, and Sanofi; and received uncompensated participation on data safety monitoring boards for Mirati Therapeutics, and Daiichi Sankyo. The remaining authors declare no conflict of interest.

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