Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission

Simple Summary Approximately 70% of patients with advanced epithelial ovarian cancer who achieve clinical remission after initial surgery and chemotherapy have a recurrence. Wilms' Tumor 1 (WT1), which is overexpressed in ovarian cancer cells, is a promising target for tumor-directed immunotherapy for ovarian cancer due to its prevalence and specificity. The aim of our open-label, non-randomized phase I study was to assess the safety of a WT1 peptide vaccine (galinpepimut-S) in combination with nivolumab in patients with WT1-expressing ovarian cancer in second or third remission. In a sample of 11 patients, the combination of galinpepimut-S vaccine and nivolumab induced immune responses and was deemed safe and tolerable. Our findings provide additional evidence that the combination of immune checkpoint inhibitors (e.g., nivolumab) and vaccines results in enhanced anti-tumor immune responses. We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms' Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti-PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade >= 3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate.