Department of Internal Medicine, Seoul National University College of Medicine & Seoul National University Hospital, Seoul, 03080, Republic of Korea.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Future Oncol. 2024;20(16):1057-1067. doi: 10.2217/fon-2023-0824. Epub 2024 Feb 13.
Neuregulin 1 () fusions are oncogenic drivers that have been detected in non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and other solid tumors. fusions are rare, occurring in less than 1% of solid tumors. Patients with fusion positive (NRG1+) cancer have limited therapeutic options. Zenocutuzumab is a novel, bispecific IgG1 antibody that targets both HER2 and HER3 proteins and inhibits NRG1 binding through a 'Dock & Block' mechanism of action. Here, we describe the rationale and design of the phase II component of the eNRGy trial, part of the overall, open-label phase I/II, multicenter trial exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC or other solid tumors.
神经调节蛋白 1()融合是致癌驱动因子，已在非小细胞肺癌（NSCLC）、胰腺导管腺癌（PDAC）和其他实体瘤中检测到。融合是罕见的，发生在不到 1%的实体瘤中。融合阳性（NRG1+）癌症患者的治疗选择有限。Zenocutuzumab 是一种新型双特异性 IgG1 抗体，靶向 HER2 和 HER3 蛋白，并通过“对接和阻断”作用机制抑制 NRG1 结合。在这里，我们描述了 eNRGy 试验的 II 期部分的原理和设计，该试验是一项开放标签的 I/II 期、多中心试验的一部分，旨在探索 zenocutuzumab 在 NRG1+ NSCLC、PDAC 或其他实体瘤患者中的安全性、耐受性、药代动力学、药效学、免疫原性和抗肿瘤活性。
