Double-Blind Randomized Phase 2 Trial Testing Personal Cancer Vaccines in Patients with Advanced Ovarian Cancer

<b>Background/Objectives:</b> Dendritic cell vaccines are a promising cancer immunotherapy. AV-OVA-1 is a patient-specific vaccine consisting of autologous dendritic cells (DCs) loaded with autologous tumor antigens (ATA) from a lysate of irradiated self-renewing cells enriched for tumor-initiating cells (TICs). A multicenter, double-blind, randomized phase 2 trial was designed to determine manufacturing feasibility, safety, and efficacy. <b>Methods:</b> Patients had newly diagnosed stage 3 or 4 ovarian cancer. Short-term cell cultures were established from freshly resected tumor specimens. Patients were screened for randomization seven months after initial diagnosis, after completing neoadjuvant and/or adjuvant chemotherapy and surgery. Eligibility included a successful cell culture, cryopreservation of sufficient monocyte numbers for differentiation into DCs, and good performance status. Patients were stratified by whether they had persistent disease; then, they were randomized 2:1 to AV-OVA-1 or autologous monocytes (MC). Cryopreserved doses of AV-OVA-1 and MC were thawed and admixed with granulocyte-macrophage colony-stimulating factor just before subcutaneous injections at weeks 1, 2, 3, 8, 12, 16, 20, and 24. <b>Results</b>: Study accrual was terminated early during the SARS-CoV-2 pandemic. Manufacturing success rates for TICs, monocyte intermediate products, and AV-OVA-1 were 70/72 (97.2%) and 47/50 (94.0%), and 29/30 (96.7%), respectively. A total of 29 participants were treated with AV-OVA-1 and 15 with MC. Patients received an average of 7.4 injections. Adverse-event frequencies were similar in both arms, mild to moderate in severity, and self-limited. T-cell immune responses increased only after AV-OVA-1. There were no survival differences in this underpowered study. <b>Conclusions:</b> AV-OVA-1 was manufactured reliably and injections were well tolerated.