title: 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.
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.
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Doreen O
authors.initials: DO
authors.lastname: Jackson
authors.affiliation: National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Byrd
authors.affiliation: Department of Surgery, Womack Army Medical Center, Fayetteville, NC, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vreeland
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Diane F
authors.initials: DF
authors.lastname: Hale
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Garth S
authors.initials: GS
authors.lastname: Herbert
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Greene
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Schneble
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Berry
authors.affiliation: Department of Surgery, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Alfred F
authors.initials: AF
authors.lastname: Trappey
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G T
authors.initials: GT
authors.lastname: Clifton
authors.affiliation: Department of Surgery, Madigan Army Medical Center, Tacoma, WA, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Hardin
authors.affiliation: Cancer Vaccine Development Program, San Antonio, TX, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Annandale, VA, USA.|Mid-Atlantic Gynecologic Oncology and Pelvic Surgical Associates, Annandale, VA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Elkas
authors.affiliation: National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Annandale, VA, USA.|Inova Schar Cancer Institute, Inova Health System, Annandale, VA, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.affiliation: National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.affiliation: National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: National Capital Consortium Fellowship in Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|Department of Obstetrics and Gynecology, Inova Fairfax Hospital Annandale, VA, USA.|Inova Schar Cancer Institute, Inova Health System, Annandale, VA, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Maxwell
authors.affiliation: Cancer Vaccine Development Program, San Antonio, TX, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
mesh_terms: D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005492:Folic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005492:Folic Acid
keywords: cancer; endometrial; folate binding protein; immunotherapy; ovarian