Exploratory phase II efficacy study of MORAb-003, a monoclonal antibody against folate receptor alpha, in platinum-sensitive ovarian cancer in first relapse

Abstract

5500 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 is a humanized monoclonal antibody to FRA. Binding of MORAb-003 to FRA blocks phosphorylation by Lyn kinase; mediates FRA-expressing tumor cell killing; and suppresses tumor growth in xenograft models. A phase 1 study of single agent (SA) MORAb-003 showed no significant AEs and suggested efficacy in platinum-resistant EOC. This study was designed to determine the efficacy of MORAb-003 as a SA, or with platinum and taxane (P/T) in recurrent, platinum-sensitive EOC. Methods: Subjects with platinum sensitive EOC in first relapse are eligible. For CA-125 elevation without symptoms (± measurable disease) the subject receives SA MORAb- 003 until progression. For symptomatic relapse or progression with SA the subject receives P/T and MORAb-003. Subjects with CR or PR receive SA MORAb-003 maintenance therapy. Results: 52 subjects have enrolled. Few drug-related adverse events have been reported with MORAb-003 alone or MORAb-003 with P/T. In subjects receiving MORAb-003 with P/T, CA-125 has normalized in 58% after 2 cycles, 88% completing 4 cycles and 100% of subjects completing 6 cycles. RECIST scores improved in parallel. Historically only 35–55% of patients treated with chemotherapy alone achieve a second remission. To date, 3/8 evaluable subjects have achieved a second remission longer than the first; 26 additional subjects are being observed for this endpoint on therapy. Subjects on SA MORAb-003 have shown transient responses of CA-125, but not complete normalization. Conclusions: MORAb-003 with P/T significantly increases ORR compared to historic data for P/T alone, and increases the duration of second compared to first remission Based on these data, additional studies of MORAb- 003 with chemotherapy in platinum-sensitive and platinum-resistant EOC are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Morphotek Morphotek Morphotek