A phase 2 Australian-New Zealand study has reported encouraging results for the combination of nivolumab and ipilimumab in women with advanced ovarian and endometrial clear cell cancers (CCCs) — rare and typically chemotherapy-resistant tumour types.
The trial, published in JAMA Oncology, enrolled 28 patients (24 ovarian CCC, 4 endometrial CCC). Most had received one prior line of therapy. Patients were treated with four induction cycles of nivolumab plus ipilimumab, followed by maintenance nivolumab.
Results were striking for this hard-to-treat group. The investigators reported an objective response rate of 54%, with three complete and eleven partial responses. At six months, progression-free survival was 58%, and the median progression-free survival was 10 months. At the time of analysis, overall survival had not yet been reached, and all responses were ongoing.
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Around one-third of patients experienced grade ≥3 immune-related adverse events, consistent with prior experience of this regimen. One patient died of immune-related myocarditis.
Exploratory analyses suggested that higher tumour mutational burden was linked with better outcomes in ovarian clear cell cases, while ARID1A mutations — common in this cancer type — were not predictive. Interestingly, all patients with TERT promoter mutations responded.
“Nivolumab combined with ipilimumab demonstrated encouraging and durable clinical activity in advanced ovarian and endometrial clear cell cancers, with manageable toxic effects consistent with other tumor types. These results warrant larger, confirmatory studies,” the authors concluded.
Clear cell ovarian and endometrial cancers are aggressive and account for 5–20% of ovarian and 5–10% of endometrial cancers, with notoriously poor responses to chemotherapy. The findings highlight the potential of immune checkpoint blockade in this group and build on signals from earlier small studies.
Paper: Gao BCarlino MSMichael M, et al. Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial. JAMA Oncol. 2025;11(9):982–989. doi:10.1001/jamaoncol.2025.1916. Access online here.
