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

5583 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 (M3) is a humanized monoclonal antibody to FRA. Binding of M3 to FRA blocks phosphorylation by Lyn kinase; mediates FRA-positive tumor cell killing; and suppresses tumor growth in xenograft models. High-dose M3 is non-toxic in monkeys. A phase 1 study showed no significant AEs and suggestions of efficacy in platinum-resistant EOC. This phase 2 efficacy study will determine the efficacy of M3 in platinum-sensitive EOC in first relapse, either as a single agent (SA) in asymptomatic relapse, or in combination with platinum and taxane (P/T) in symptomatic relapse, and to maintain a second response. Methods: Subjects with EOC in first relapse are eligible. For CA125 elevation without symptoms (± measurable disease) the subject receives SA M3 until progression. For symptomatic relapse the subject receives P/T and M3. Subjects with CR or PR receive SA M3 maintenance therapy with the objective of prolonging the second remission longer than the first. Endpoints include CA125 and CT scans. ORR and PFS will be determined for each arm. Results: To date, 15 subjects have been treated, 8 in combination therapy and 7 on single-agent M3. No significant drug-related adverse events have been reported. All subjects treated with the combination of M3 and P/T for symptomatic relapse who have reached at least the first evaluation point have achieved a normalization of CA125 and reduction of tumor size (CR or PR) by CT scan using RECIST criteria, including 3 of 3 subjects with first remissions of 6 to 9 months. Early responses have been observed in the SA M3 treatment arm. Conclusions: This first phase 2 study will determine the efficacy of M3, either as SA or in combination with P/T chemotherapy to achieve a meaningful response rate in EOC in first relapse, and to maintain the second remission longer than the subject’s own first remission. These data will be used to define the most effective phase of disease in which to use M3, and to focus a pivotal study on the area of greatest efficacy. The early results continue to demonstrate activity of M3 in EOC. No significant financial relationships to disclose.