Personalized neoantigen-targeting cancer vaccines in ovarian cancer: a phase 1 trial

Journal article

Personalized neoantigen-targeting cancer vaccines (PCV) in the adjuvant setting are of increasing interest across malignancies. Herein, we report the results of a first-in-disease phase I clinical trial testing the feasibility and safety of PCV for high-grade epithelial ovarian cancer (HGOC). ‘NeoVax’ consisted of pools of synthetic long peptides targeting patient-specific neoantigens admixed with the immunostimulant polyICLC, was combined with delayed administration of anti-PD-1 antibody, and was tested in 10 patients (one newly diagnosed patient (Cohort A) and 9 patients at first recurrence (Cohort B)) with platinum-sensitive OC following standard-of-care (SOC) 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 non-invasive cell-free DNA analysis despite a median of 6.5 months from the time of diagnostic biopsy to vaccine administration, during which patients received SOC chemotherapy. Biomarker analysis was suggestive of biologic activity of the vaccine in 6 of 10 patients and this was associated with broader tumor and vaccine-specific immune responses in blood and tumor 58 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 appeared to dictate clinical efficacy following vaccination.
ClinicalTrials.gov Identifier: 62 NCT04024878

Authors: Sellars, MC; Frank, JA; Shim, B; Vanasse, A; Wu, C

• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Medicine
• Acceptance date: 2026-09-17
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English