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

• Published in: Oncotarget Vol. 8; no. 9; pp. 15912 - 15923
• Main Authors: Jackson, Doreen O, Byrd, Kevin, Vreeland, Timothy J, Hale, Diane F, Herbert, Garth S, Greene, Julia M, Schneble, Erika J, Berry, John S, Trappey, Alfred F, Clifton, G T, Hardin, Mark O, Martin, Jonathan, Elkas, John C, Conrads, Thomas P, Darcy, Kathleen M, Hamilton, Chad A, Maxwell, George L, Peoples, George E
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 28.02.2017
• Subjects: Aged; Carrier Proteins - genetics; Clinical Research Paper; Endometrial Neoplasms - genetics; Female; Folic Acid; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Humans; Immunotherapy - methods; Middle Aged; Ovarian Neoplasms - genetics; cancer; endometrial; ovarian; folate binding protein; immunotherapy
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.13305

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. 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. 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). 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.