Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (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
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引用次数: 0
Abstract
Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.
Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR). Patients received intravenous amivantamab 1050 mg (1400 mg if ≥80 kg) plus oral lazertinib 240 mg.
Results: In Cohort A (n=162), investigator-assessed ORR was 28% (95% CI, 22-36). Blinded independent central review (BICR)-assessed ORR was 35% (95% CI, 27-42), with median duration of response (DoR) of 8.3 months (95% CI, 6.7-10.9) and clinical benefit rate of 58% (95% CI, 50-66). At a median follow-up of 12 months, 32/56 responders (57%) achieved a DoR ≥6 months. Median progression-free survival by BICR 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-anti-tumor activity was reported among 7 patients with baseline brain lesions and no prior brain radiation/surgery. Exploratory biomarker analyses using circulating tumor DNA next-generation sequencing showed responses in patients with and without identified EGFR/MET-dependent resistance. Most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). Most common grade ≥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+lazertinib demonstrated anti-tumor activity with a safety profile characterized by EGFR/MET-realated adverse events, which were generally manageable.
期刊介绍：
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
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