A phase II study in newly diagnosed stage III/IV epithelial ovarian cancer evaluating carboplatin/taxol/pembrolizumab in patients receiving neoadjuvant chemotherapy followed by pembrolizumab maintenance with or without olaparib.

BACKGROUND: Pembrolizumab, a PD-1 immune checkpoint inhibitor, has shown promise in various cancers, but its role in ovarian cancer remains under investigation. While the current standard of care (SOC) is initially effective for epithelial ovarian cancer (EOC), approximately 70% of patients relapse within 3 years of completing upfront treatment, highlighting an unmet need for therapies that extend time to first progression. The survival benefit observed with hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery (IDS), combined with the potential for checkpoint inhibitors to augment antitumor immunity alongside cytotoxic and hyperthermic stimuli, provides the rationale for this novel trial combining neoadjuvant chemotherapy (NACT), immunotherapy, and HIPEC in the upfront treatment of advanced EOC. PATIENTS AND METHODS: This double-arm, open-label phase II trial plans to enroll 40 patients. Patients with histologically confirmed diagnosis of FIGO stage III or IV EOC who is a candidate for neoadjuvant chemotherapy with planned IDS are eligible. Patients will receive pembrolizumab 200 mg in combination with carboplatin and paclitaxel for 3 21-day treatment cycles prior to IDS and 3 treatment cycles following IDS. During IDS, the first 10 patients who are eligible for HIPEC will receive 100 mg/m2 of cisplatin heated to 40-42 °C intraperitoneally over 90 min. All patients will continue 2 years of maintenance pembrolizumab, and BRCA1/2-mutated or homologous recombination deficient patients will also receive maintenance olaparib in combination with pembrolizumab. CONCLUSION: The findings may inform future clinical development of primary and maintenance treatment strategies in advanced epithelial ovarian cancer. NCT#: 05952453.