A phase I dose escalation study of AGS-8M4 (ASP6183), an anti-AGS-8 fully human antibody, in advanced ovarian cancer.

Abstract

5059 Background: AGS-8M4 (ASP6183) is an IgG1k fully human monoclonal antibody (MAb) directed to AGS-8, a novel cell surface protein expressed on tumor cells in patients with ovarian cancer. In xenograft mouse models, AGS-8M4 inhibited tumor growth and prolonged survival. Methods: Women with recurrent disease or stage III/IV advanced ovarian cancer who had received at least one prior platinum containing regimen were treated. AGS-8M4 was administered by IV infusion over 1 hour every 2 weeks (Q2W) for four doses in cohorts of 3-6 subjects at doses of 1, 5, 10 and 20 mg/kg. Disease assessments were performed every 8 weeks. Subjects with stable disease (SD) were eligible to receive 4 additional doses of AGS-8M4 in extended treatment at the same dose and schedule. SD was defined as no new onset or worsening of symptoms or measureable disease (per RECIST). The primary endpoints of the study were safety and pharmacokinetics (PK). Secondary endpoints included immunogenicity and anti-tumor activity. Results: Of the 15 women who received AGS-8M4, 11 completed the 4 planned treatment doses, 2 withdrew early and 2 are still receiving treatment. One subject (10 mg/kg) with a history of thrombocytopenia had a dose-limiting toxicity (DLT) due to thrombocytopenia; however, the cohort was expanded and no further DLTs were experienced. One subject in the 20 mg/kg cohort who had SD is receiving AGS-8M4 extended therapy. No deaths, infusion-related toxicities, or anti-AGS-8M4 antibodies have been reported. PK results from doses up to 20 mg/kg indicate linear PK. Decline in serum concentration of AGS-8M4 was biphasic. The terminal half-life of AGS-8M4 (t1/2lz) ranged from 2 to 3 weeks. The median accumulation ratio for AGS-8M4 Q2W dosing ranged from 1.5 to 1.9 weeks. AUC and Cmax increased proportionally with increase in doses from 1 to 20 mg/kg. Conclusions: AGS-8M4 was well tolerated at all dose levels. Based on the results of this study, a phase Ib study of AGS-8M4 in combination with two different chemotherapy regimens has been initiated and phase II combination studies are planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agensys, Inc., Astellas Pharma Agensys, Inc. Agensys, Inc., Astellas Pharma Agensys, Inc.