Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A

Benjamin Besse; Koichi Goto; Yongsheng Wang; Se-Hoon Lee; Melina E Marmarelis; Yuichiro Ohe; Reyes Bernabe Caro; Dong-Wan Kim; Jong-Seok Lee; Sophie Cousin; Eiki Ichihara; Yongsheng Li; Luis Paz-Ares; Akira Ono; Rachel E Sanborn; Naohiro Watanabe; Maria Jose de Miguel; Carole Helissey; Catherine A Shu; Alexander I Spira; Pascale Tomasini; James Chih-Hsin Yang; Yiping Zhang; Enriqueta Felip; Frank Griesinger; Saiama N Waqar; Antonio Calles; Joel W Neal; Christina S Baik; Pasi A Jänne; S Martin Shreeve; Joshua C Curtin; Bharvin Patel; Michael Gormley; Xuesong Lyu; Jun Chen; Pei-Ling Chu; Janine Mahoney; Leonardo Trani; Joshua M Bauml; Meena Thayu; Roland E Knoblauch; Byoung Chul Cho

doi:10.1016/j.jtho.2024.12.029

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Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A

Authors: Benjamin Besse ; Koichi Goto ; Yongsheng Wang ; Se-Hoon Lee ; Melina E Marmarelis ; Yuichiro Ohe ; Reyes Bernabe Caro ; Dong-Wan Kim ; Jong-Seok Lee ; Sophie Cousin ; Eiki Ichihara ; Yongsheng Li ; Luis Paz-Ares ; Akira Ono ; Rachel E Sanborn ; Naohiro Watanabe ; Maria Jose de Miguel ; Carole Helissey ; Catherine A Shu ; Alexander I Spira ; Pascale Tomasini ; James Chih-Hsin Yang ; Yiping Zhang ; Enriqueta Felip ; Frank Griesinger ; Saiama N Waqar ; Antonio Calles ; Joel W Neal ; Christina S Baik ; Pasi A Jänne ; S Martin Shreeve ; Joshua C Curtin ; Bharvin Patel ; Michael Gormley ; Xuesong Lyu ; Jun Chen ; Pei-Ling Chu ; Janine Mahoney ; Leonardo Trani ; Joshua M Bauml ; Meena Thayu ; Roland E Knoblauch ; Byoung Chul Cho

Citation: JOURNAL OF THORACIC ONCOLOGY, Vol.20(5) : 651-664, 2025-05

Journal Title: JOURNAL OF THORACIC ONCOLOGY

ISSN: 1556-0864

Issue Date: 2025-05

MeSH: Acrylamides / administration & dosage ; Acrylamides / pharmacology ; Acrylamides / therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Aniline Compounds / pharmacology ; Aniline Compounds / therapeutic use ; Antibodies, Bispecific ; Antineoplastic Combined Chemotherapy Protocols* / therapeutic use ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Carcinoma, Non-Small-Cell Lung* / pathology ; Cohort Studies ; Disease Progression ; ErbB Receptors / genetics ; Female ; Humans ; Indoles ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Lung Neoplasms* / pathology ; Male ; Middle Aged ; Morpholines* / therapeutic use ; Mutation ; Pyrimidines ; Survival Rate

Keywords: Amivantamab ; Biomarker analyses ; Lazertinib ; NSCLC

Abstract: Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib.

Results: In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22-36). The blinded independent central review-assessed ORR was 35% (95% CI: 27-42), with a median duration of response of 8.3 months (95% CI: 6.7-10.9) and a clinical benefit rate of 58% (95% CI: 50-66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1-5.8); median overall survival was 14.8 months (95% CI: 12.2-18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).

Conclusions: For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable.