EP294 - PHASE 1/2 STUDY OF GALINPEPIMUT-S PLUS PEMBROLIZUMAB COMBINATION IN PATIENTS WITH WT1+ PLATINUM-RESISTANT OVARIAN CANCER IN 2ND/3RD LINE OF THERAPY (ID 363)
- Roisin O'Cearbhaill (United States of America)
- Jarrod P. Holmes (United States of America)
- Bruno R. Bastos (United States of America)
- Siqing Fu (United States of America)
- Reid M. Muenzen (United States of America)
- Julia W. Cohen (United States of America)
- Dragan Cicic (United States of America)
- Sami Ali (United States of America)
Abstract
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.
