Abstract CT073: Comparing an attenuated booster (E39’) vs E39 booster to potentiate the clinical benefit of the folate binding protein (FBP)-derived vaccine (E39 + GM-CSF) in a phase I/IIa trial to prevent recurrence in endometrial (EC) and ovarian cancer (OC) patients
Authors: Jackson Doreen O. , Vreeland Timothy J. , Hale Diane F. , Herbert Garth S. , Greene Julia M. , Schneble Erika J. , Berry John S. , Trappey Alfred F. , Clifton Guy T. , Elkas John C. , Hamilton Chad , Darcy Kathleen M. , Maxwell George L. , Peoples George E. 
Published: July 2016

Abstract
Background: We have completed treatment in a phase I/IIa trial utilizing E39 (GALE-301, FBP 191-199, EIWTHSYKV), an HLA-A2 restricted, FBP-derived peptide + GM-CSF vaccine to prevent recurrence in EC and OC patients (pts). This vaccine has been shown to be safe and immunogenic, with promising early clinical results. Booster inoculations have improved disease-free survival (DFS) in our previous peptide vaccine trials, but repeated boosting can theoretically lead to overstimulation and loss of vaccine-induced T cells. To avoid this, we have developed an attenuated version of E39, E39’ (GALE-302, EIWTFSTKV), which has been shown to expand FBP-specific cytolytic T cells in vitro and in vivo. Therefore to assess this strategy, E39-vaccinated pts from the phase I/IIa trial were randomized to receive a booster series of either E39’ or E39 + GM-CSF and compared for safety, immunologic response, and DFS.
Methods: HLA-A2+ pts were vaccinated (VG), and HLA-A2- pts were followed as controls (CG). Six monthly intradermal inoculations of E39 + 250mcg GM-CSF were administered to the VG to complete the primary vaccine series (PVS). Patients were then randomized to receive 2 booster inoculations of 500mcg of E39’ or E39 + 250mcg GM-CSF at 6 (B1) and 12 (B2) months post-PVS. Local reactions (LR) were recorded 48-72 hours after each booster. Demographic, safety, immunologic, and DFS data were collected and evaluated with the appropriate statistical tests.
Results: A total of 51 pts were enrolled; 29 in VG and 22 in CG. 17 pts continued on to the booster series and were randomized. For B1, 9 received E39’ and 8 received E39; B2 included 7 pts in each group. There were no significant clinicopathologic differences between groups. No difference in toxicities were seen with no grade 3 or 4 toxicities in either group. The average LR for the E39’ vs E39 groups were 79.7+14.0 mm vs 82.1+8.3 mm, respectively for B1 (p = 0.45) and 74.1+11.5 mm vs 78+11.2 mm, respectively for B2 (p = 0.41). Clinically, the recurrence rate was 22.2% in the E39’ boost group vs 25% for E39. The estimated 2-year DFS for B1 pts for E39’, E39 and the CG were 66.7%, 58.3%, and 36.0%, respectively; and for B2 pts were 66.7%, 66.7%, and 36.0%. Comparing just the boosted groups, for B1 the hazard ratio (HR) for E39’ vs E39 = 0.71 (95% CI: 0.1 - 5.13), and for B2 the HR for E39’ vs E39 = 0.82 (95% CI: 0.05 - 13.24).
Conclusion: The use of an attenuated peptide (E39’) booster was safe and as immunogenic as the wildtype peptide (E39) in this randomized trial of optimal boosting strategies. More importantly, there appears to be a potential clinical advantage to the attenuated booster in this small trial. These results must be corroborated by further evaluation of this attenuated peptide vaccine and boosting strategy in a larger clinical trial.
Citation Format: Doreen O. Jackson, Timothy J. Vreeland, Diane F. Hale, Garth S. Herbert, Julia M. Greene, Erika J. Schneble, John S. Berry, Alfred F. Trappey, Guy T. Clifton, John C. Elkas, Chad Hamilton, Kathleen M. Darcy, George L. Maxwell, George E. Peoples. Comparing an attenuated booster (E39’) vs E39 booster to potentiate the clinical benefit of the folate binding protein (FBP)-derived vaccine (E39 + GM-CSF) in a phase I/IIa trial to prevent recurrence in endometrial (EC) and ovarian cancer (OC) patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT073.