Phase 2 pembrolizumab PD-1 antibody plus TLR3 agonist rintatolimod and autologous αDC1 vaccine

This Phase 2, nonrandomized, sequential-design neoadjuvant study at UPMC Hillman Cancer Center tests whether “locoregional chemoimmunotherapy” can improve immune activation and clinical outcomes in chemo-naive stage III–IV ovarian cancer. Patients receive intraperitoneal (IP) cisplatin (DNA crosslinker) with intravenous paclitaxel (microtubule stabilizer), followed by an IP chemokine-modulatory regimen that includes rintatolimod (TLR3 agonist dsRNA) plus interferon alfa-2b (type I interferon immune cytokine), along with oral celecoxib (COX-2 inhibitor) to shape inflammatory signaling. Systemic pembrolizumab (Keytruda; Merck/MSD) is added to block PD-1 and reduce T-cell exhaustion, and one arm adds intradermal autologous αDC1 dendritic-cell vaccines (a personalized cellular vaccine platform) before interval debulking surgery and subsequent therapy. The key angle is the heavy emphasis on peritoneal, immune-directed “conditioning” plus checkpoint blockade—trying to turn a typically immunologically “cold” peritoneal disease compartment more inflamed and T-cell–permissive. Today’s care for advanced-stage ovarian cancer in the neoadjuvant setting is platinum-taxane chemotherapy followed by interval cytoreductive surgery, then completion chemotherapy and (in many patients) maintenance therapy such as PARP inhibition when BRCA/HRD-positive and/or bevacizumab in selected cases; this trial explores whether adding IP innate stimulation + interferon signaling + PD-1 blockade + a dendritic-cell vaccine can deepen response before surgery.