Amivantamab Plus Lazertinib in Atypical <i>EGFR</i> -Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2
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-naïve 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-naïve 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 αC-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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (57)
Benjamin Besse
Alexander I. Spira
Virginia Cancer Specialists and NEXT Oncology-Virginia, Fairfax
Joel W. Neal
Koichi Goto
Christina S. Baik
Thoracic, Head and Neck Medical Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle
Melina E. Marmarelis
Jong-Seok Lee
Zacharias Anastasiou
Johnson & Johnson, Athens, Greece
Joshua C. Curtin
Johnson & Johnson, Spring House, PA
Xuesong Lyu
Johnson & Johnson, Shanghai, China
Janine Mahoney
Johnson & Johnson, Spring House, PA
Levon Demirdjian
Johnson & Johnson, San Diego, CA
Craig S. Meyer
Johnson & Johnson, Brisbane, CA
Youyi Zhang
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Institute of Advanced Clinical Medicine, Peking University; National Health Commission (NHC) Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Beijing Key Laboratory of Cardiovascular Receptors Research; Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing 100191, China (H.G., Y.L., Y.X., M.Z., L.B., H.C., W.Z., W.X., K.W., Y.D., X.Y., H.W., J.H., E.D., Y. Zhang, H.X.).
Isabelle Leconte
Johnson & Johnson, Allschwil, Switzerland
Patricia Lorenzini
Johnson & Johnson, Raritan, NJ
Roland E. Knoblauch
Johnson & Johnson, Spring House, PA
Leonardo Trani
Johnson & Johnson, Spring House, PA
Mahadi Baig
Johnson & Johnson, Raritan, NJ
Joshua M. Bauml
Johnson & Johnson, Spring House, PA
Gee-Chen Chang
School of Medicine and Institute of Medicine, Chung Shan Medical University and Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
Byoung Chul Cho
Sophie Cousin
Institut Bergonié, Bordeaux, NA, France
Jiuwei Cui
Giuseppe Curigliano
Gianluca Del Conte
Xiaorong Dong
Enriqueta Felip
Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona
Pilar Garrido
Ramón y Cajal University Hospital, Madrid, Spain
Nicolas Girard
Institut Curie, Institut du Thorax Curie-Montsouris, Paris
Adriano Gravina
Frank Griesinger
Department of Hematology and Oncology, Pius Hospital, University Medicine Oldenburg, Oldenburg, Germany
Matthew Gubens
Eric Haura
Eiki Ichihara
Dong-Wan Kim
School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 02841, Republic of Korea
Se Hyun Kim
Se-Hoon Lee
Yongsheng Li
Department of Chemistry, State Key Lab of Molecular Engineering of Polymers, and Shanghai Key Lab of Molecular Catalysis and Innovative Materials
Shun Lu
Melina Marmarelis
Sebastian Michels
Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen Köln Bonn Düsseldorf, University of Cologne, Cologne, Germany
Joel Neal
Jorge Nieva
Luis Paz-Ares
Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid
Niels Reinmuth
Thoracic Oncology, Asklepios Clinics Munich-Gauting, Gauting, Germany
Yuki Sato
Alexander Spira
NEXT Oncology Virgina, Virgina Cancer Specialists Research Institute, Fairfax
Meili Sun
Central Hospital Affiliated to Shandong First Medical University, Jinan, China
Pascale Tomasini
Aix Marseille University – CNRS, INSERM, CRCM; CEPCM – AP-HM Hôpital de la Timone, Marseille, France
Yongsheng Wang
Division of Thoracic Tumor Multimodality Treatment Cancer Center, West China Hospital, Sichuan University
Marcel Wiesweg
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
Lin Wu
The Department of Thoracic Medical Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China
James Chih-Hsin Yang
National Taiwan University Hospital, NTU Cancer Center, Taipei
Yu Yao
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering
Yiping Zhang
Minglei Zhuo
Department of Thoracic Oncology I, Beijing Cancer Hospital, Beijing, China