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.

Autor: Tsimberidou AM; 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. atsimber@mdanderson.org., Grothey A; Gastrointestinal Cancer Research at West Cancer Center and Research Institute, Germantown, TN, USA., Sigal D; Scripps Clinic and Scripps Cancer Center, La Jolla, CA, USA., Lenz HJ; Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Hochster HS; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA., Chao Y; Taipei Veterans General Hospital, Taipei, Taiwan., Bai LY; China Medical University Hospital, Taichung City, Taiwan., Yen CL; National Cheng Kung University Hospital, Tainan, Taiwan., Xu D; OBI Pharma USA, Inc, San Diego, CA, USA., Saville MW; OBI Pharma USA, Inc, San Diego, CA, USA.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2024 Dec; Vol. 94 (6), pp. 787-798. Date of Electronic Publication: 2024 Sep 23.
DOI: 10.1007/s00280-024-04714-z
Abstrakt: 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.
Competing Interests: Declarations Competing interests Apostolia Maria Tsimberidou: Clinical Trial Research Funding (received through the institution): OBI Pharma, Agenus, Vividion, Macrogenics, AbbVie, IMMATICS, Novocure, Tachyon, Parker Institute for Cancer Immunotherapy, Tempus, and Tvardi; fees for consulting or advisory roles for Avstera Therapeutics, Bioeclipse, BrYet, Diaccurate, Macrogenics, NEX-I, and VinceRx. Dong Xu and M. Wayne Saville are employees of OBI Pharma USA, Inc. The remaining authors declare no relevant conflict of interest.
(© 2024. The Author(s).)
Databáze: MEDLINE
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