Site Editor
Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Friday, August 1, 2025
Based on the results of the multicenter nonrandomized phase II MoST-CIRCUIT trial, which were published in JAMA Oncology, combination immunotherapy with the anti–PD-1 antibody nivolumab and the anti–CTLA-4 antibody ipilimumab demonstrated significant clinical activity in patients with advanced gynecologic clear cell cancers. Oliver Klein, MD, of Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Australia, and colleagues also reported durable responses.
Patients with advanced clear cell ovarian cancer (n = 24) or clear cell endometrial cancer (n = 4) who received up to one course of prior systemic therapy were enrolled. They were intravenously administered 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for four doses (induction phase), followed by 480 mg of nivolumab alone every 4 weeks (maintenance phase).
Overall, the objective response rate was 54%; this included 3 (12%) and 12 (42%) patients with complete and partial responses, respectively. The objective response rate was 55% in patients with clear cell ovarian cancer and 50% in those with clear cell endometrial cancer. According to the investigators, the median duration of response has not been reached, with all responses ongoing. The 6-month progression-free survival rate was 58%, and the median overall survival has not been reached. Nine patients (35%) experienced a grade 3 or 4 immune-related adverse event; grade 5 myocarditis was documented in one patient.
“Further clinical trials are needed to confirm the efficacy of anti–PD-1/CTLA-4 combination immunotherapy in a larger patient population with recurrent disease and to compare it with combination therapies of anti–PD-1 blockade and an antiangiogenic agent,” the investigators concluded. “Ongoing biomarker research is currently underway to better define the patient population that is responsive to this treatment regimen and define the mechanism of treatment resistance.”
Disclosure: Dr. Klein reported no conflicts of interest. For full disclosures of the other study authors, visit jamanetwork.com.
