Clinical Research Papers:
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
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Abstract
Doreen O. Jackson1, Kevin Byrd2,3, Timothy J. Vreeland4, Diane F. Hale1, Garth S. Herbert1, Julia M. Greene1, Erika J. Schneble1, John S. Berry1, Alfred F. Trappey1, Guy Travis Clifton5, Mark O. Hardin6, Jonathan Martin7, John C. Elkas8,9, Thomas P. Conrads2,3,8,10, Kathleen M. Darcy2,3, Chad A. Hamilton2,3, George L. Maxwell2,3,8,10 and George E. Peoples7
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.
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