Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial
- Author(s)
- Gao, B; Carlino, MS; Michael, M; Underhill, C; Marshall, H; Gunjur, A; So, J; Kee, D; Antill, Y; Lam, WS; Chan, H; Harrup, R; Hamilton, A; Grady, J; Ballinger, M; Tavancheh, E; Yoon, WH; Palmer, J; Thomas, D; Wilkie, K; Cebon, J; Klein, O;
- Journal Title
- JAMA Oncology
- Publication Type
- Online publication before print
- Abstract
- IMPORTANCE: Gynecological clear cell cancers (CCCs) are aggressive malignant neoplasms with low response rate to chemotherapy. The treatment of patients with metastatic disease remains an area of significant unmet need. OBJECTIVE: To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade using nivolumab and ipilimumab in advanced gynecological CCCs. DESIGN, SETTING, AND PARTICIPANTS: The MoST-CIRCUIT prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced selected rare cancers. Patients with advanced clear cell ovarian cancer (CCOC)/clear cell endometrial cancer (CCEC) with a maximum of 1 course of prior systemic therapy were enrolled from August 2021 to February 2024 across 17 Australian and New Zealand sites. INTERVENTIONS: Patients received nivolumab, 3 mg/kg, and ipilimumab, 1 mg/kg, every 3 weeks for 4 doses followed by nivolumab, 480 mg, every 4 weeks for 96 weeks until disease progression or the development of unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: Coprimary end points were objective response rate (ORR) and 6-month progression-free survival (PFS) as assessed by RECIST version 1.1 criteria, with the secondary end points being median overall survival, PFS, and treatment-related toxic effects. RESULTS: Of 28 included patients, the median (range) age was 55 (34-77) years. A total of 24 had CCOC and 4 had CCEC; 19 (68%) had a previous course of therapy. Overall ORR was 54% (95% CI, 35-71), with 3 (12%) with complete response and 12 (42%) with partial response; the ORR was 55% (95% CI, 35-73) in the CCOC group and 50% (95% CI, 9-91) in the CCEC group. The median duration of response has not been reached, with all responses ongoing. The 6-month PFS was 58% (95% CI, 39-74), and the median overall survival has not been reached. A total of 9 patients (35%) experienced a grade 3 or 4 immune-related adverse event, and a grade 5 myocarditis occurred in 1 patient. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, immunotherapy using combined anti-PD-1/CTLA-4 blockade demonstrated encouraging activity with a high rate of durable responses in patients with advanced gynecological CCCs. This regimen should be further investigated in this patient population with unmet medical need. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04969887.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1001/jamaoncol.2025.1916
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-07-25 07:49:13
Last Modified: 2025-07-29 05:57:05