Recently, Vigil showed significant clinical benefit with improvement in relapse free (RFS) and overall survival (OS) in pre-planned subgroup analysis in stage III/IV newly diagnosed ovarian cancer patients with BRCA wild type (BRCA-wt) molecular profile. Here we analyze homologous recombination (HR) status of patients enrolled in the Phase 2b VITAL study and determine clinical benefit of Vigil in HR proficient (P) patients. Patients were previously enrolled in a Phase 2b, double-blind, placebo-controlled trial. All were in complete response with Stage III/IV high grade serious, endometroid or clear cell ovarian cancer. HR status was determined using MyChoice®CDx score (<42 = HRP) (Myriad Genetics, Inc., UT). Post-hoc analyses were carried out using Kaplan Meier and restricted mean survival time (RMST) analysis to evaluate RFS and OS based on HR deficiency (D) status. RFS was improved with Vigil (n = 25) in HRP patients compared to placebo (n = 20) (HR = 0.386; 90% CI 0.199–0.750; p = 0.007), results were verified by RMST (p = 0.017). Similarly, OS benefit was observed in Vigil group compared to placebo (HR = 0.342; 90% CI 0.141–0.832; p = 0.019). Results with OS were also verified with RMST (p = 0.008). Vigil exhibited clinical benefit in HRP molecular profile patients. •Limited treatment options exist for homologous recombination proficient ovarian cancer.•Vigil is an anticancer immuno-therapeutic.•Vigil provides neoantigen education, GMCSF activation and TGFβ suppression reversal.•Vigil vs. placebo shows benefit of RFS and OS (HR = 0.386, p = 0.007; HR = 0.342, p = 0.019).•Vigil demonstrated no Grade 3/4 toxicity compared to placebo.