The 2 year DFS estimate is 24.8% (CG) v 91.7% (1000 mcg pts) (p=0.02). OUTSTANDING RESULTS!!
Preliminary results of the phase I/IIa dose finding trial of a folate binding protein vaccine (E39+GM-CSF) in ovarian and endometrial cancer patients to prevent recurrence
Session title: Gynaecological Cancer
Session type: Poster Session
Track: Gynaecological Cancer
Abstract number: 2764
Abstract title:
Preliminary results of the phase I/IIa dose finding trial of a folate binding protein vaccine (E39+GM-CSF) in ovarian and endometrial cancer patients to prevent recurrence
J.M. Greene(1), E.J. Schneble(1), J.S. Berry(1), A.F. Trappey(1), G.T. Clifton(2), K. Darcy(3), J.C. Elkas(4), C.A. Hamilton(5), G.L. Maxwell(6), G.E. Peoples(7)
(1)San Antonio Military Medical Center, General Surgery, San Antonio, TX, USA
(2)MD Anderson Cancer Center, Surgical Oncology, Houston, TX, USA
(3)Department of Defense Gynecologic Cancer Center of Excellence Women's Health Integrated Research Center at Inova Health System/Inova Fairfax Hospital, Gynecologic Oncology, Annandale, VA, USA
(4)Mid-Atlantic Gynecologic Oncology and Pelvic Surgical Associates, Gynecologic Oncology, Annandale, VA, USA
(5)Department of Defense Gynecologic Cancer Center of Excellence Women's Health Integrated Research Center at Inova Health System/Inova Fairfax Hospital, Gynecologic Oncology, Bethesda, MD, USA
(6)Department of Defense Gynecologic Cancer Center of Excellence Women's Health Integrated Research Center at Inova Health System/Inova Fairfax Hospital, Gynecologic Oncology, Falls Church, VA, USA
(7)Cancer Vaccine Development Program/Cancer Insight/Galena Consultant, Surgical Oncology, Bethesda, MD/San Antonio, TX, USA
Background: Folate Binding Protein (FBP) (aka Folate Receptor-a) is an immunogenic protein over-expressed in endometrial (EC) and ovarian cancer (OC). We are conducting a phase I/IIa trial with E39, an HLA-A2-restricted, FBP-derived peptide + GM-CSF vaccine. E39 is given adjuvantly to prevent clinical recurrences (CR) in disease-free high-risk, EC and OC patients (pts) after standard-of-care therapy (SOC). Here, we summarize toxicity, in vivo immunologic responses, and disease-free survival (DFS) in this dose-finding trial.
Materials and Methods: This trial began as a 3×3, dose-escalation (100, 500, 1000 mcg of E39), safety phase I trial and transitioned to a phase IIa comparing expanded dose cohorts. Disease-free EC and OC pts were enrolled after SOC. HLA-A2+ pts were vaccinated (VG), and HLA-A2- pts followed prospectively as a control group (CG). 6 monthly intradermal inoculations of E39 + 250 mcg GM-CSF are administered followed by 2 boosters every 6 months. Demographic, safety, immunologic, and CR data are being collected. In vivo immunologic response is measured by the orthogonal mean of a delayed type hypersensitivity reaction (DTH) to the E39 peptide without GM-CSF placed remote from the primary vaccination site. DFS is compared by Kaplan-Meir and logrank tests. Continuous variables are compared with analysis of variance and proportions with Fisher's exact test.
Results: 51 pts were enrolled; 29 in the VG (15 pts 1000mcg v 14 pts <1000mcg) and 22 in the CG. There are no differences in age, grade, stage, or histology between groups (all p=0.1). E39 is well-tolerated and safe with no >grade 3 toxicities and no differences in toxicities based on dose. DTH increased pre- to post-vaccination (5.9mm+1.5 v 11.7mm+3.2, p=0.08). DTH increase was larger in 1000 mcg pts (3.8mm v 17.8mm, p=0.06) v <1000 mcg pts (8mm v 11mm, p=0.56). With 9.3 months median follow-up, CR rate is 38% (VG) v 50% (CG), p=0.41. Among 1000 mcg pts, there is only one CR (6.7% v 50% CG, p=0.01). The 2 year DFS estimate is 24.8% (CG) v 91.7% (1000 mcg pts) (p=0.02).
Conclusions: This phase I/IIa trial reveals that E39 + GM-CSF is well-tolerated and elicits a strong and dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This dose-finding study proves the safety and establishes the dose of E39 for a prospective, randomized, GM-CSF controlled, late stage trial in HLA-A2+ EC and OC patients to prevent recurrence.
Trial Number: NCT01580696
Conflict of interest: Other Substantive Relationships: George Peoples is a consultant to and stockholder of Galena. He holds partial patent rights and royalties to E39.
