Abstract B007: Improved disease-free survival in endometrial and ovarian cancer patients with low folate binding protein expression after treatment with the E39 peptide vaccine in a Phase I/IIa trial

Introduction: One of the most encouraging examples of targeted therapy for cancer is trastuzumab, but its success is dependent on levels of expression of its target, HER2. We have found that HER2 expression levels also have a significant impact on the efficacy of HER2-directed peptide vaccines. Analogous to HER2 in breast cancer, Folate Binding Protein (FBP) is over-expressed on ovarian and endometrial cancer cells (up to 80 - 90-fold higher) and increased FBP expression is associated with aggressive disease. As a result, multiple FBP-directed therapies are being developed. We are investigating E39 + GM-CSF, which is an HLA-A2-restricted FBP-derived peptide vaccine used to prevent recurrence in disease-free endometrial and ovarian cancer patients (pts) after standard of care (SOC), multi-modality therapy. We have shown that E39 is safe, effectively generates E39-specific immune responses, and may improve DFS when optimally dosed in a phase I/IIa trial.1 Little is known about the effects of FBP expression levels on FBP-directed therapies, including our E39 vaccine. Purpose: Here, we report clinical outcomes of patients based on FBP expression levels from a phase I/IIa trial of the E39+GM-CSF vaccine given for the prevention of recurrence in disease-free endometrial and ovarian cancer patients. Methods: Disease-free, HLA-A2+ pts were vaccinated (VG), while HLA-A2- pts were followed as untreated controls (CG). The VG received 6 monthly inoculations of E39+GM-CSF, including either 100, 500, or 1000mcg of peptide and 250mcg of GM-CSF. FBP expression testing was performed by immunohistochemistry and the results were graded 0-4+ based on the percentage of positively staining cells. Patient's tumors were then categorized as low expression (FBPlo) if scored 0-1+ or high expression (FBPhi) if 2-4+. The pts were monitored for evidence of clinical recurrence through the SOC follow-up by their treating oncology team. Demographics, FBP expression and disease-free survival (DFS) were analyzed using appropriate statistical tests. Results: Thirty-eight enrolled pts underwent FBP expression testing (CG n = 20; VG n = 18). There were no clinicopathologic differences between groups (p≥0.1). Nineteen pts were found to be FBPlo (CG, n = 11; VG, n = 8) and 19 were FBPhi (CG, n = 9; VG, n = 10). Median follow up was 16.3 months. There was no significant difference in overall DFS between the CG and the VG (34.6% vs. 34.6%, p = 0.208). In FBPlo pts, there was improved DFS in the VG