start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=JCO-24-02835 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non?Small Cell Lung Cancer: Results From CHRYSALIS-2 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose For patients with advanced non?small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.
Patients and Methods CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ?2 previous lines of therapy. Participants were treatment-na?ve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ?80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).
Results As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-na?ve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and ƒ¿C-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.
Conclusion In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals. en-copyright= kn-copyright= en-aut-name=TomasiniPascale en-aut-sei=Tomasini en-aut-mei=Pascale kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=WangYongsheng en-aut-sei=Wang en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiYongsheng en-aut-sei=Li en-aut-mei=Yongsheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FelipEnriqueta en-aut-sei=Felip en-aut-mei=Enriqueta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WuLin en-aut-sei=Wu en-aut-mei=Lin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=CuiJiuwei en-aut-sei=Cui en-aut-mei=Jiuwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=BesseBenjamin en-aut-sei=Besse en-aut-mei=Benjamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SpiraAlexander I. en-aut-sei=Spira en-aut-mei=Alexander I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NealJoel W. en-aut-sei=Neal en-aut-mei=Joel W. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GotoKoichi en-aut-sei=Goto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=BaikChristina S. en-aut-sei=Baik en-aut-mei=Christina S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MarmarelisMelina E. en-aut-sei=Marmarelis en-aut-mei=Melina E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ZhangYiping en-aut-sei=Zhang en-aut-mei=Yiping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=LeeJong-Seok en-aut-sei=Lee en-aut-mei=Jong-Seok kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=LeeSe-Hoon en-aut-sei=Lee en-aut-mei=Se-Hoon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YangJames Chih-Hsin en-aut-sei=Yang en-aut-mei=James Chih-Hsin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MichelsSebastian en-aut-sei=Michels en-aut-mei=Sebastian kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=AnastasiouZacharias en-aut-sei=Anastasiou en-aut-mei=Zacharias kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=CurtinJoshua C. en-aut-sei=Curtin en-aut-mei=Joshua C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=LyuXuesong en-aut-sei=Lyu en-aut-mei=Xuesong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=MahoneyJanine en-aut-sei=Mahoney en-aut-mei=Janine kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=DemirdjianLevon en-aut-sei=Demirdjian en-aut-mei=Levon kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MeyerCraig S. en-aut-sei=Meyer en-aut-mei=Craig S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=ZhangYouyi en-aut-sei=Zhang en-aut-mei=Youyi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=LeconteIsabelle en-aut-sei=Leconte en-aut-mei=Isabelle kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=LorenziniPatricia en-aut-sei=Lorenzini en-aut-mei=Patricia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=KnoblauchRoland E. en-aut-sei=Knoblauch en-aut-mei=Roland E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=TraniLeonardo en-aut-sei=Trani en-aut-mei=Leonardo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=BaigMahadi en-aut-sei=Baig en-aut-mei=Mahadi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=BaumlJoshua M. en-aut-sei=Bauml en-aut-mei=Joshua M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=ChoByoung Chul en-aut-sei=Cho en-aut-mei=Byoung Chul kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= affil-num=1 en-affil=Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM H?pital de La Timone kn-affil= affil-num=2 en-affil=Division of Thoracic Tumor Multimodality Treatment, Cancer Center and Clinical Trial Center, West China Hospital, Sichuan University kn-affil= affil-num=3 en-affil=Chongqing University Cancer Hospital kn-affil= affil-num=4 en-affil=Medical Oncology Service, Vall dfHebron Institute of Oncology (VHIO), Vall dfHebron Barcelona Hospital Campus, Universitat Aut?noma de Barcelona kn-affil= affil-num=5 en-affil=Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University kn-affil= affil-num=6 en-affil=The First Hospital of Jilin University kn-affil= affil-num=7 en-affil=Paris-Saclay University, Institut Gustave Roussy kn-affil= affil-num=8 en-affil=Virginia Cancer Specialists kn-affil= affil-num=9 en-affil=Stanford Cancer Institute, Stanford University kn-affil= affil-num=10 en-affil=National Cancer Center Hospital East kn-affil= affil-num=11 en-affil=University of Washington Fred Hutchinson Cancer Research Center kn-affil= affil-num=12 en-affil=Perelman School of Medicine, University of Pennsylvania kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=14 en-affil=Zhejiang Cancer Hospital kn-affil= affil-num=15 en-affil=Seoul National University College of Medicine and Seoul National University Hospital kn-affil= affil-num=16 en-affil=Samsung Medical Center, Sungkyunkwan University School of Medicine kn-affil= affil-num=17 en-affil=National Taiwan University Cancer Center kn-affil= affil-num=18 en-affil=Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen K?ln Bonn D?sseldorf, University of Cologne kn-affil= affil-num=19 en-affil=Johnson & Johnson kn-affil= affil-num=20 en-affil=Johnson & Johnson kn-affil= affil-num=21 en-affil=Johnson & Johnson kn-affil= affil-num=22 en-affil=Johnson & Johnson kn-affil= affil-num=23 en-affil=Johnson & Johnson kn-affil= affil-num=24 en-affil=Johnson & Johnson kn-affil= affil-num=25 en-affil=Johnson & Johnson kn-affil= affil-num=26 en-affil=Johnson & Johnson kn-affil= affil-num=27 en-affil=Johnson & Johnson kn-affil= affil-num=28 en-affil=Johnson & Johnson kn-affil= affil-num=29 en-affil=Johnson & Johnson kn-affil= affil-num=30 en-affil=Johnson & Johnson kn-affil= affil-num=31 en-affil=Johnson & Johnson kn-affil= affil-num=32 en-affil=Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine kn-affil= END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=e2400228 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240919 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Response to Imatinib in a Patient With Gastric Adenocarcinoma With KIT Q556_K558 In-Frame Deletion: A Case Report en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=NinomiyaKiichiro en-aut-sei=Ninomiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EnnishiDaisuke en-aut-sei=Ennishi en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkamotoKunio en-aut-sei=Okamoto en-aut-mei=Kunio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AndoMidori en-aut-sei=Ando en-aut-mei=Midori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NakamuraSatoko en-aut-sei=Nakamura en-aut-mei=Satoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TomidaShuta en-aut-sei=Tomida en-aut-mei=Shuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AyadaYoshiyuki en-aut-sei=Ayada en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakimotoGo en-aut-sei=Makimoto en-aut-mei=Go kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IchiharaEiki en-aut-sei=Ichihara en-aut-mei=Eiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OkitaNatsuko en-aut-sei=Okita en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=ToyookaShinichi en-aut-sei=Toyooka en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TabataMasahiro en-aut-sei=Tabata en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=2 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Medical Oncology, Kagawa Prefectural Central Hospital kn-affil= affil-num=4 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital, kn-affil= affil-num=5 en-affil=Department of Pathology, Kagawa Prefectural Central Hospital kn-affil= affil-num=6 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pathology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Research Management Division, Clinical Research Support Office, National Cancer Center Hospital kn-affil= affil-num=11 en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Center for Clinical Oncology, Okayama University Hospital kn-affil= END