人表皮生长因子受体2（HER2）阳性转移性乳腺癌（MBC）的预后目前仍不理想，需要更多的抗HER2药物。在这里，我们报告了一项第I期研究，评估了LZM005，一个HER2抗体，作为单药治疗或与曲妥珠单抗加多西他赛联合使用对HER2阳性MBC患者的安全性、活性和生物标志物。2017年10月至2019年12月，共有34名患者接受了LZM005治疗（14例单药治疗，20例联合治疗）。未观察到DLT。Ia期常见的不良事件（AEs）包括腹泻（21.4%）、输注反应（21.4%）和高三酰甘油血症（21.4%），而Ib期的AEs包括白细胞减少症（85.0%）、中性粒细胞减少症（75.0%）、贫血症（60.0%）、腹泻（60.0%）和皮疹/瘙痒症（50.0%）。所有的AEs都是可管理的。在Ia期，有1例病例（1/14，总体反应率[ORR]：7.1%）达到部分缓解（PR）；疾病控制率为42.90%（6/14）。在Ib期，11名患者（55.0%）达到了PR，8名患者（40.0%）有稳定疾病。ORR在曲妥珠单抗未治疗组和治疗组分别为100%（6/6）和35.7%（5/14）。生物标志物分析表明，染色质重塑基因KMT2B和BRWD1与更好的无进展生存有关。LZM005在HER2阳性MBC患者中耐受性良好且显示出强效活性。©2022.作者。

The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC.© 2022. The Author(s).