Amivantamab Plus Lazertinib in Atypical EGFR -Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2

作者：Pascale Tomasini, Yongsheng Wang, Yongsheng Li, Enriqueta Felip, Lin Wu, Jiuwei Cui, Benjamin Besse, Alexander I. Spira, Joel W. Neal, Kōichi Goto, Christina S. Baik, Melina E. Marmarelis, Eiki Ichihara, Yiping Zhang, Jong‐Seok Lee, Se‐Hoon Lee, James Chih‐Hsin Yang, Sebastian Michels, Zacharias Anastasiou, Joshua C. Curtin, Xuesong Lyu, James Mahoney, Levon Demirdjian, Craig S. Meyer, Youyi Zhang, Isabelle Leconte, Patricia Lorenzini, Roland E. Knoblauch, Leonardo Trani, Mahadi Baig, Joshua Bauml, Byoung Chul Cho, Gee‐Chen Chang, Byoung Chul Cho, Sophie Cousin, Jiuwei Cui, Giuseppe Curigliano, Gianluca Del Conte, Xiaorong Dong, Enriqueta Felip, Pilar Garrido, Nicolas Girard, Adriano Gravina, Frank Griesinger, Matthew A. Gubens, Eric B. Haura, Eiki Ichihara, Dong-Wan Kim, Se Hyun Kim, Se‐Hoon Lee, Yongsheng Li, Shun Lu, Melina E. Marmarelis, Sebastian Michels, Joel W. Neal, Jorgé Nieva, Luis Paz‐Ares, Niels Reinmuth, Yuki Sato, Alexander I. Spira, Meili Sun, Pascale Tomasini, Yongsheng Wang, Marcel Wiesweg, Lin Wu, James Chih‐Hsin Yang, Yu Yao, Yiping Zhang, Minglei Zhuo · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-24-02835 · 被引用次数：5 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

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 parti...