Work

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

Year: 2026

Type: article

Abstract: Objective 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. Methods iPRIME is an open label, non-comparative multicentre phase 2 study. Patients with FIGO stage IIIC and IV high grade serous carcinomawere 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, with a rate exceeding 50% considered positive. Secondary endpoints included the CRS 3 rate in each arm, progression-free survival, and radiological response. Results 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%). The CRS 3 rate by central review was higher in Du-T-NACT than in NACT (27% [13/49] versus 3.8% [1/26], p = 0.03), but this was not reflected in other measures of clinical benefit. Radiological response after treatment by RECIST 1.1 was similar between arms (45% versus 50%, p = 0.82), as was CA-125 response by GCIG criteria (80% versus 81%). Median progression-free survival was 14.7 months in both arms, with no difference in PFS at 12 or 24 months (p = 0.64). Conclusion Combining durvalumab and tremelimumab to neoadjuvant carboplatin–paclitaxel did not achieve the primary efficacy endpoint. This was the first study to utilise 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.

Source: Cancer Immunology Immunotherapy

DOI: 10.1007/s00262-026-04589-4