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.

IF 21 1区 医学 Q1 ONCOLOGY Journal of Thoracic Oncology Pub Date : 2025-01-02 DOI:10.1016/j.jtho.2024.12.029
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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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.

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Amivantamab + Lazertinib治疗egfr突变的非小细胞肺癌(NSCLC)患者在接受奥西替尼和铂基化疗进展后的疗效:来自CHRYSALIS-2队列A的结果
简介:表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者在奥西替尼和铂基化疗后病情进展的治疗选择有限。方法:chrysaly -2队列A评估了amivantamab+lazertinib对EGFR外显子19缺失或l858r突变的NSCLC患者在奥西替尼和铂基化疗后疾病进展的治疗效果。主要终点是研究者评估的客观缓解率(ORR)。患者静脉注射amivantamab 1050mg(≥80kg则1400mg)加口服lazertinib 240mg。结果:在队列A (n=162)中,研究者评估的ORR为28% (95% CI, 22-36)。盲法独立中心评价(BICR)评估的ORR为35% (95% CI, 27-42),中位缓解持续时间(DoR)为8.3个月(95% CI, 6.7-10.9),临床获益率为58% (95% CI, 50-66)。在中位随访12个月时,32/56名应答者(57%)的DoR≥6个月。BICR的中位无进展生存期为4.5个月(95% CI, 4.1-5.8);中位总生存期为14.8个月(95% CI, 12.2-18.0)。在7例基线脑病变且既往无脑放射/手术的患者中报告了中枢神经系统抗肿瘤活性的初步证据。使用循环肿瘤DNA下一代测序的探索性生物标志物分析显示,有或没有确定的EGFR/ met依赖性耐药的患者均有反应。最常见的不良事件是皮疹(分组术语;81%),输液相关反应(68%)和甲沟炎(52%)。最常见的≥3级治疗相关不良事件是皮疹(分组术语;10%),输液相关反应(9%)和低白蛋白血症(6%)。结论:对于治疗选择有限的患者,amivantamab+lazertinib显示出抗肿瘤活性,其安全性以EGFR/ met相关不良事件为特征,这些不良事件通常是可控的。
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来源期刊
Journal of Thoracic Oncology
Journal of Thoracic Oncology 医学-呼吸系统
CiteScore
36.00
自引率
3.90%
发文量
1406
审稿时长
13 days
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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A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET). Impact of comorbidities on the mortality benefits of lung cancer screening: a post-hoc analysis of PLCO and NLST trials. A Prospective Phase II Trial of First-Line Osimertinib for Patients With EGFR Mutation-Positive NSCLC and Poor Performance Status (OPEN/TORG2040). 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. Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From TROPiCS-03.
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