Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A.
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN
1556-1380
Date Issued
2025-01-02
Author(s)
Besse, Benjamin
Goto, Koichi
Wang, Yongsheng
Lee, Se-Hoon
Marmarelis, Melina E
Ohe, Yuichiro
Bernabe Caro, Reyes
Kim, Dong-Wan
Lee, Jong-Seok
Cousin, Sophie
Ichihara, Eiki
Li, Yongsheng
Paz-Ares, Luis
Ono, Akira
Sanborn, Rachel E
Watanabe, Naohiro
de Miguel, Maria Jose
Helissey, Carole
Shu, Catherine A
Spira, Alexander I
Tomasini, Pascale
Zhang, Yiping
Felip, Enriqueta
Griesinger, Frank
Waqar, Saiama N
Calles, Antonio
Neal, Joel W
Baik, Christina S
Jänne, Pasi A
Shreeve, S Martin
Curtin, Joshua C
Patel, Bharvin
Gormley, Michael
Lyu, Xuesong
Chen, Jun
Chu, Pei-Ling
Mahoney, Janine
Trani, Leonardo
Bauml, Joshua M
Thayu, Meena
Knoblauch, Roland E
Cho, Byoung Chul
Abstract
Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.
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.
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%).
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.
Subjects
Amivantamab
Biomarker analyses
Lazertinib
NSCLC
SDGs
Type
journal article