In an Australian–New Zealand phase II trial (MoST-CIRCUIT) reported in JAMA Oncology, Gao et al found that the combination of nivolumab and ipilimumab showed “encouraging activity” in patients with advanced ovarian and endometrial clear cell cancers.
Study Details
Twenty-eight patients with advanced clear cell ovarian cancer (CCOC; n = 24) or clear cell endometrial cancer (CCEC; n = 4) with a maximum of one course of prior systemic therapy were enrolled in the multicenter trial between August 2021 and February 2024. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for four doses followed by nivolumab at 480 mg every 4 weeks for 96 weeks or until disease progression or unacceptable toxicity. The co-primary endpoints were objective response rate and 6-month progression-free survival.
Key Findings
Among all patients, objective response was observed in 15 (54%, 95% confidence interval [CI] = 35%–71%), with complete response in 3 (12%). Objective response rates were 55% (95% CI = 35%–73%) in the CCOC group and 50% (95% CI = 9%–91%) in the CCEC group. Median duration of response has not been reached; all responses were ongoing at the time of analysis (range = 9–33 months).
Among all patients, 6-month progression-free survival was 58% (95% CI = 39%–74%). With a median follow-up of 11.2 months (95% CI = 1.05–17.3 months), median progression-free survival was 10 months (95% CI = 2–17 months). Median overall survival was not reached.
Immune-related adverse events of any grade occurred in 78% of patients; grade 3 or 4 events were observed in 10 (35%), most commonly hepatitis (n = 3, 11%). Death due to immune-related myocarditis occurred in one patient.
The investigators concluded: “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 [clear cell cancers]. This regimen should be further investigated in this patient population with unmet medical need.”
Oliver Klein, MD, of Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Victorian Government Operational Infrastructure Support Program. For full disclosures of all study authors, visit jamanetwork.com.
