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
{"title":"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。","authors":"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","doi":"10.1007/s00280-024-04714-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":" ","pages":"787-798"},"PeriodicalIF":2.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573804/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1007/s00280-024-04714-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment.</p>\",\"PeriodicalId\":9556,\"journal\":{\"name\":\"Cancer Chemotherapy and Pharmacology\",\"volume\":\" \",\"pages\":\"787-798\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573804/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Chemotherapy and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00280-024-04714-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Chemotherapy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00280-024-04714-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.
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.
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