Personalized neoantigen-targeting cancer vaccines in the adjuvant setting are of increasing interest across malignancies. Here we report the results of a phase 1 clinical trial testing the feasibility and safety of personalized neoantigen-targeting cancer vaccines for high-grade epithelial ovarian cancer. 'NeoVax' consisted of pools of synthetic long peptides targeting patient-specific neoantigens admixed with the immunostimulant poly-ICLC, was combined with delayed administration of anti-PD-1 antibody, and was tested in ten patients (one newly diagnosed patient (Cohort A) and nine patients at first recurrence (Cohort B)) with platinum-sensitive ovarian cancer following standard-of-care platinum doublet chemotherapy. Nine of 12 evaluable Cohort B patients were vaccinated (75%, 90% CI 47-93%) and 1 of 9 Cohort A patients (11%, 90% CI 0.6-43%). No unexpected safety signals were encountered and no patients discontinued treatment due to toxicity. Across patients, >70% selected targets remained detectable by noninvasive cell-free DNA analysis despite a median of 6.5 months from the time of diagnostic biopsy to vaccine administration, during which, patients received standard-of-care chemotherapy. Biomarker analysis was suggestive of biologic activity of the vaccine in six of ten patients and this was associated with broader tumor and vaccine-specific immune responses in blood and tumor following vaccination. Resistant tumor clones reflected diverse mechanisms affecting antigen presentation, indicative of immune-selective pressure exerted by vaccination. Overall, the interplay between the repertoire of antigens presented by the tumor and the breadth of induced immunity seemed to dictate clinical efficacy following vaccination. ClinicalTrials.gov identifier: NCT04024878.