Neoadjuvant Chemotherapy with Dual Immune Checkpoint Inhibitors for Advanced-Stage Ovarian Cancer: Final Analysis of TRU-D Phase II Nonrandomized Clinical Trial

Purpose: This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival, and neoadjuvant outcomes of neoadjuvant chemotherapy (NAC) combined with dual immune checkpoint inhibitors in advanced-stage epithelial ovarian cancer (EOC). Patients and Methods: Between June 2019 and July 2021, 45 patients with unresectable stage III to IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate after NAC, a chemotherapy response score, pathologic complete response, overall survival, and safety. The preplanned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pretreatment tumors. Results: The 12-month PFS rate was 65.9% [95% confidence interval (CI), 52.8–not estimated (NE)], whereas the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7–NE) and 36.4% (95% CI, 24.7–NE), respectively. After NAC, the objective response rate was 86.7%, whereas 14 patients (31.1%) had a chemotherapy response score of three, and five (11.1%) achieved pathologic complete response. The 30-month overall survival rate was 87.7%. The most common grade ≥3 adverse event was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (combined positive score) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes. Conclusions: NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.