Interim analysis of a phase I/IIa trial assessing E39+GM-CSF, a folate binding protein vaccine, to prevent recurrence in ovarian and endometrial cancer patients

// Doreen O. Jackson 1 , Kevin Byrd 2,3 , Timothy J. Vreeland 4 , Diane F. Hale 1 , Garth S. Herbert 1 , Julia M. Greene 1 , Erika J. Schneble 1 , John S. Berry 1 , Alfred F. Trappey 1 , Guy Travis Clifton 5 , Mark O. Hardin 6 , Jonathan Martin 7 , John C. Elkas 8,9 , Thomas P. Conrads 2,3,8,10 , Kathleen M. Darcy 2,3 , Chad A. Hamilton 2,3 , George L. Maxwell 2,3,8,10 and George E. Peoples 7 1 Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA 2 National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center Bethesda, MD, USA 3 Gynecologic Cancer Center of Excellence, Annandale, VA, USA 4 Department of Surgery, Womack Army Medical Center, Fayetteville, NC, USA 5 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department of Surgery, Madigan Army Medical Center, Tacoma, WA, USA 7 Cancer Vaccine Development Program, San Antonio, TX, USA 8 Department of Obstetrics and Gynecology, Inova Fairfax Hospital Annandale, VA, USA 9 Mid-Atlantic Gynecologic Oncology and Pelvic Surgical Associates, Annandale, VA, USA 10 Inova Schar Cancer Institute, Inova Health System, Annandale, VA, USA Correspondence to: Doreen O. Jackson, email: // Keywords : cancer, ovarian, endometrial, folate binding protein, immunotherapy Received : July 01, 2016 Accepted : October 19, 2016 Published : November 11, 2016 Abstract BACKGROUND: Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date. METHODS: HLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated. RESULTS: This trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p ≥ 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.7±1.5 mm vs 10.3±3.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.8±2.0 mm vs 9.5±3.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG ( p = 0.021). CONCLUSIONS: This phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.