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

作者：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 Venancio A; Moro Ana M; Bla**alg Roberto; Scott Andrew M; Hoffman Eric W

来源：Gynecologic Oncology, 2015, 138(2): 272-277.

DOI：10.1016/j.ygyno.2015.05.023

• platinum resistant/refractory ovarian cancer
• Anti Lewis-Y monoclonal antibody (hu3S193)

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/m(2) 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.

• 出版日期2015-8