Phase I-II study of OBI-888, a humanized monoclonal IgG1 antibody against the tumor-associated carbohydrate antigen Globo H, in patients with advanced solid tumors.

IF 2.7 4区医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI:10.1007/s00280-024-04714-z

Apostolia Maria Tsimberidou, Axel Grothey, Darren Sigal, Heinz-Josef Lenz, Howard S Hochster, Yee Chao, Li-Yuan Bai, Chia-Jui L Yen, Dong Xu, M Wayne Saville

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Abstract

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.

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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 OBI-888 在晚期实体瘤患者中的 I-II 期研究。

目的：OBI-888是一种特异于肿瘤相关碳水化合物抗原Globo H的人源化单克隆IgG1抗体：方法：在A部分（"3 + 3 "设计）中，患者每周接受5、10或20毫克/千克的OBI-888静脉注射治疗；在B部分（西蒙两阶段设计）中，患者每周接受20毫克/千克的OBI-888静脉注射治疗（1个周期=28天）：共有54名患者接受了治疗（A部分，14人；B部分，40人）。在所有研究剂量中，OBI-888均安全且耐受性良好，与OBI-888相关的治疗突发不良事件发生率较低。未达到OBI-888的最大耐受剂量。在20毫克/千克剂量水平（第二阶段推荐剂量）以下，未发现剂量限制性毒性反应。A部分和B部分分别有28.6%和20%的患者病情稳定（SD），其中有3名患者病情稳定时间分别为6个月、7个月和9个月。每次OBI-888治疗后都会诱导抗体依赖性细胞毒性（ADCC）（A部分和B部分的平均增幅分别为3.8倍和4.7倍），这表明ADCC诱导是OBI-888的一种潜在作用机制：结论：OBI-888的耐受性良好。结论：OBI-888的耐受性良好，有3名患者的SD延长。每次OBI-888治疗后都能诱导ADCC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Chemotherapy and Pharmacology 医学-药学

CiteScore

6.10

自引率

3.30%

发文量

116

审稿时长

2.5 months

期刊介绍： Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.