Department of Investigational Cancer Therapeutics, Katherine Russell Dixie Distinguished Endowed Professor, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Gastrointestinal Cancer Research at West Cancer Center and Research Institute, Germantown, TN, USA.
Cancer Chemother Pharmacol. 2024 Dec;94(6):787-798. doi: 10.1007/s00280-024-04714-z. Epub 2024 Sep 23.
PURPOSE: OBI-888 is a humanized, monoclonal IgG1 antibody specific to the tumor-associated carbohydrate antigen Globo H. We conducted a phase I-II study of OBI-888 in patients with advanced cancer. METHODS: Patients were treated with OBI-888 5, 10, or 20 mg/kg IV weekly in Part A ("3 + 3" design) and 20 mg/kg IV weekly in Part B (Simon's 2-stage design) (1 cycle = 28 days). RESULTS: Overall, 54 patients were treated (Part A, n = 14; Part B, n = 40). OBI-888 was safe and well tolerated across the doses studied, with a low incidence of OBI-888-related treatment emergent adverse events. The maximum tolerated dose of OBI-888 was not reached. No dose-limiting toxicities were noted up to the 20 mg/kg dose level (recommended phase 2 dose). Stable disease (SD) was noted in 28.6% and 20% of Parts A and B, respectively, including three patients with SD for 6+, 7+, and 9 months. Antibody-dependent cellular cytotoxicity (ADCC) was induced after each OBI-888 treatment (average increase, 3.8-fold and 4.7-fold in Parts A and B, respectively), suggesting that ADCC induction is a potential mechanism of action of OBI-888. CONCLUSIONS: OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment.
目的：OBI-888 是一种针对肿瘤相关碳水化合物抗原 Globo H 的人源化单克隆 IgG1 抗体。我们在晚期癌症患者中进行了 OBI-888 的 I- II 期研究。
方法：患者在 A 部分（“3+3”设计）中接受 OBI-888 5、10 或 20mg/kg IV 每周一次治疗，在 B 部分（Simon 的 2 期设计）中接受 20mg/kg IV 每周一次治疗（1 个周期=28 天）。
结果：共有 54 名患者接受治疗（A 部分，n=14；B 部分，n=40）。OBI-888 在研究剂量范围内安全且耐受良好，与 OBI-888 相关的治疗出现的不良事件发生率较低。未达到 OBI-888 的最大耐受剂量。在 20mg/kg 剂量水平（推荐的 2 期剂量）上未观察到剂量限制性毒性。A 部分和 B 部分的分别有 28.6%和 20%的患者观察到疾病稳定（SD），包括 3 名患者的 SD 持续时间为 6+、7+和 9 个月。在每次 OBI-888 治疗后均诱导了抗体依赖性细胞毒性（ADCC）（A 部分和 B 部分的平均增加分别为 3.8 倍和 4.7 倍），表明 ADCC 诱导是 OBI-888 的潜在作用机制。
结论：OBI-888 耐受良好。三名患者出现了长时间的疾病稳定。在每次 OBI-888 治疗后均诱导了 ADCC。
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