A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma

• Published in: Gynecologic oncology Vol. 138; no. 2; pp. 272 - 277
• Main Authors: Smaletz, Oren, Diz, Maria D.P.E, do Carmo, Claudio C, Sabbaga, Jorge, Cunha-Junior, Geraldo F, Azevedo, Sergio J, Maluf, Fernando C, Barrios, Carlos H, Costa, Ronaldo L, Fontana, Ana G, Madrigal, Vivian, Wainstein, Alberto J, Yeda, Fernanda P, Alves, Venâncio A, Moro, Ana M, Blasbalg, Roberto, Scott, Andrew M, Hoffman, Eric W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2015
• Subjects: Adult; Aged; Anti Lewis-Y monoclonal antibody (hu3S193); Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - pharmacokinetics; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms - immunology; Fallopian Tube Neoplasms - metabolism; Fallopian Tube Neoplasms - therapy; Female; Hematology, Oncology and Palliative Medicine; Humans; Lewis Blood-Group System - immunology; Middle Aged; Neoplasms, Glandular and Epithelial - immunology; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - therapy; Obstetrics and Gynecology; Organoplatinum Compounds - pharmacology; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - therapy; Peritoneal Neoplasms - immunology; Peritoneal Neoplasms - metabolism; Peritoneal Neoplasms - therapy; platinum resistant/refractory ovarian cancer; Young Adult; Anti Lewis-Y monoclonal antibody (hu3S193); platinum resistant/refractory ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2015.05.023

Abstract Objectives The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. Methods This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). Results 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24 + weeks [clinical benefit rate 23% (95% CI = 9.77%–46.71%)]. Median PFS was 8.4 weeks (95% CI = 6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p = 0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). Conclusions Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.