Introduction Galinpepimut-S (GPS) is an HLA-unrestricted heteroclitic peptide vaccine against Wilms Tumor-1 (WT1), an antigen highly expressed in ovarian cancer (OC). GPS has shown promising activity as maintenance therapy in combination with checkpoint blockade in patients with OC in 2nd/3rd remission. We investigated GPS plus pembrolizumab in patients with measurable WT1+ platinum-resistant OC relapsed after or refractory to 1st/2nd -or later- line of therapy.

Methods GPS (800 mcg)/GM-CSF (70 mcg) were administered subcutaneously Q3Weeks on D1CycleX, Cycles 1–2, followed by GPS/GM-CSF plus pembrolizumab 200 mg intravenously Q3Weeks Cycles 3–6. After an unpaired pembrolizumab administration at Week 18, the combination resumed Q3Weeks Cycles 7–12, per protocol. Primary endpoints were safety and overall response rate (ORR). Exploratory endpoints were PFS, OS and immune response.

Results Safety: N=25, GPS alone=8 (due to disease progression); >1 dose of combination =17. Median age: 64-yrs; median number of prior lines: 2. Five patients experienced 11 SAEs, one of which was drug related. No DLTs. Only known toxicities of either drug were observed. Efficacy: N=16: ORR=6.3% (versus 11.5% in comparable patients given pembrolizumab alone in KEYNOTE-028); disease control rate (ORR + stable disease) was 50% with a 14.4-month median follow-up. Median PFS and OS were 2.8 and 18.4 months, respectively versus 1.9 and 13.8 months in KEYNOTE-028, correspondingly. Immune response: N=14: post-GPS increments in WT1-reactive CD8/CD4 cell frequencies in 42.8%/85.7% of patients.

Conclusion/Implications GPS/pembrolizumab combination was safe & highly immunogenic and showed modest clinical benefit in patients with measurable advanced platinum-resistant OC, warranting further investigation.