Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

Abstract

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives

“…Then, the humanized version hu3S193 was constructed, demonstrating potent immune effector function, with higher ADCC and CDC than its murine counterpart [260]. In clinical studies, it demonstrated itself to be safe, with a strong ability to target tumors, justifying further investigation [57,261] (NCT00084799). However, in a phase II study in gynecological cancers (NCT00617773), the clinical benefit of hu3S193 was modest [58].…”

ABO(H) and Lewis blood group substances and disease treatment

“…This suggested that the drug is expected to be a part of combined immunotherapy and chemotherapy. However, a phase II trial with hu3S193 for the treatment of ovarian, it did not show sufficient activity and with some treatment‐related adverse events such as fatigue, nausea and vomiting 66,67 . More data are needed to investigate the efficacy and safety of hu3S193.…”

A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer

“…All these studies suggested that Lewis Y was a promising target for the therapy of epithelial cancers including ovarian, breast, and gastric cancers. Lewis Y has been evaluated as a target in several clinical trials using monoclonal antibody (mAb), antibody-drug conjugate (ADC), and chimeric antigen receptor T-Cell immunotherapy (CAR-T); however, a limited clinical benefit has been achieved so far from these trials [30,31].…”