Neoadjuvant durvalumab and tremelimumab in combination with chemotherapy in newly diagnosed advanced high-grade serous ovarian cancer (iPRIME): a randomized, non-comparative phase 2 trial using chemotherapy response score as the primary endpoint

To determine the efficacy of neoadjuvant dual immune checkpoint blockade with durvalumab and tremelimumab in combination with carboplatin and paclitaxel (Du-T-NACT), defined by the chemotherapy response score (CRS) 3 rate after three cycles of treatment, in newly diagnosed advanced-stage high-grade serous ovarian, fallopian tube or peritoneal carcinoma. iPRIME is an open label, non-comparative multicentre phase 2 study. Patients with FIGO stage IIIC and IV high-grade serous carcinoma were randomized 2:1 to receive durvalumab and tremelimumab in combination with carboplatin and paclitaxel (Du-T-NACT) or standard neoadjuvant carboplatin and paclitaxel alone (NACT). The primary endpoint was CRS 3 rate in Du-T-NACT. Secondary endpoints included the CRS 3 rate in each arm, progression-free survival, and radiological response. 40/49 (81.6%) of patients in Du-T-NACT were evaluable for chemotherapy response score. The rate of CRS 3 in Du-T-NACT was 13/40 (32, 90% CI 20–47%), which did not meet the pre-specified primary endpoint. Radiological response after treatment by RECIST 1.1 was similar between arms (45% vs. 50%, p = 0.82), as was CA-125 response by GCIG criteria (80% vs. 81%) were similar between arms. Median progression-free survival was 14.7 months in both arms, with no difference in PFS at 12 or 24 months ( p = 0.64). Combining durvalumab and tremelimumab to neoadjuvant carboplatin–paclitaxel did not achieve the primary efficacy endpoint. This was the first study to utilize CRS 3 as a primary endpoint in the frontline treatment of ovarian cancer. Further research is required to assess the role of neoadjuvant dual blockade immunotherapy with chemotherapy in advanced ovarian cancer and identify biomarkers of response.