Final Report of a Randomized Phase 1b Trial to Assess Sequencing of the E39 and E39′ Vaccines to Optimize Long-term Antitumor Immunity in Folate Binding Protein (FBP)-Expressing Breast and Ovarian Tumors

John W Myers, MD¹, Kaitlin M Peace, MD¹, Timothy J Vreeland, MD², Diane F Hale, MD¹, Doreen O Jackson, MD¹, Julia M Greene, MD¹, Tommy A Brown, MD¹, Guy T Clifton, MD¹, George E Peoples, MD³, Elizabeth A Mittendorf, MD, PhD². ¹Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, TX, ²The University of Texas MD Anderson Cancer Center, Houston, TX, ³Cancer Vaccine Development Program, San Antonio, TX

OBJECTIVES: E39 (FBP191-199,GALE-301,EIWTHSYKV) is a FBP-derived peptide vaccine shown to be safe and efficacious in a phase I/IIa trial.  Due to concerns of overstimulation with repeated inoculations of one peptide, we developed an attenuated version, E39’(GALE-302,EIWTFSTKV), shown in vitro to enhance E39-specific immunity. Here, we present the final analysis of different vaccine doses/schedules to induce FBP immunity.

METHODS: Disease-free, HLA-A2+ breast (BC, n=35) or ovarian (OC, n=4) cancer patients (pts) were enrolled and randomized to three primary vaccine series (PVS) arms: EE (monthly E39x6); EE’ (E39x3, E39’x3); E’E E39’x3, E39x3). Delayed-type hypersensitivity (DTH) and E39-specific cytotoxic T-lymphocytes (CTL) were assessed throughout the study.  This data was used to assess significant residual immunity (SRI), and patients were sorted into: with SRI (SRI) and without (nSRI). Patients within these groups were randomized to one booster of either E39(E) or E39’(E’). Immunologic and safety data were analyzed.

RESULTS: 30 pts completed the PVS [EE(10),EE’(10),E’E(10)], 28 received boosters [EE-E(5),EE-E’(5), EE’-E(7), EE’-E’(3), E’E-E(3),E’E-E’(5)]. No clinicopathologic differences or related toxicities >grade 2 were appreciated.  There was only an increase in DTH pre- to 6-months post-PVS in the EE’ arm (ΔEE=-7mm, p=0.16; ΔEE’=+33.75mm, p=0.001; ΔE’E=-0.64mm, p=0.48).  There was no difference in DTH pre- to 6-months post-booster among booster groups, however at 1-month post-booster, the EE’-E patients had increased DTH (ΔEE’E=39.43,p=0.02).

CONCLUSION: Both peptides were noted to be safe and immunogenic. The in vivo DTH response was enhanced with the PVS sequence of E39 then E39’, and seems best paired with an E39 booster; this may indicate expansion of effective clonal populations of CD8+ T cells with this strategy.  Further analysis of this combination’s effect on recurrence in a larger phase II trial is justified.

Presented at the SAGES 2017 Annual Meeting in Houston, TX.

Abstract ID: 87878

Program Number: MSS04

Presentation Session: Full-Day Military Surgical Symposium – Basic Science Presentations

Presentation Type: MSSPodium