Background: FRα is overexpressed on > 90% of high-grade EOC. We conducted a randomized double-blind multicenter phase II clinical trial to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF adjuvant) versus GM-CSF alone as a control in patients with stage III-IV high-grade platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma in first complete or partial remission, irrespective of baseline level of FRα expression. Methods: Patients with stage III-IV high-grade serous, high-grade endometrioid, carcinosarcoma or poorly differentiated EOC who had previously completed standard upfront therapy without evidence of disease progression and who were within a year of last platinum were randomized 1:1 to intradermal vaccination of TPIV200 versus intradermal GM-CSF alone. The vaccination period included 6 administrations of the study drug at 4-week intervals. Up to 6 booster vaccinations at 12-week intervals were permitted for patients who did not have disease progression. AEs were assessed using CTCAE. Tumor response was assessed via RECIST every 12 weeks. The primary endpoint, progression free survival (PFS), was calculated from date of first vaccination to the date of progression, death or study termination. Results: Of 120 patients randomized, 63 (53%) were treated on the TPIV200 arm. The median age at study entry was 63 years (range 37-88). AEs were generally mild. Injection site reaction was more frequent in the TPIV200 (63%) versus GM-CSF arm (39%). The other most common AEs, abdominal pain (25%) and fatigue (23%), were comparable in both arms. At study termination with a median follow-up of 15.2 months (range: 1.2-28.3 months), 68 of 119 intention-to-treat patients had progressed (55% in the TPIV200 arm and 59% in the GM-CSF arm). The median PFS was 11.1 months (95% CI: 8.3-16.6 months) and there was no statistically significant difference in median PFS between the arms (10.9 months with TPIV200 versus 11.1 months with GM-CSF, HR = 0.85 [upper 90% CI = 1.17]). Conclusions: Although TPIV200 had a manageable safety profile, the study was terminated for futility after the planned interim analysis. Future development of FRα-targeted therapy will likely focus on the careful selection of patients whose cancers show high FRα expression. Clinical trial information: NCT02978222