{"entity":{"id":"paper-nct04969887-jama-oncol-2025","kind":"paper","name":"Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial","aka":[],"tldr":"Published report from the MOST-CIRCUIT trial registered as NCT04969887, in JAMA Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"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.\n\nObjective: 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.\n\nDesign, 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.\n\nInterventions: 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.\n\nMain 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.\n\nResults: 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.\n\nConclusions 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.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04969887.\n\nIndexed on Europe PMC as PubMed record 40608313 (DOI 10.1001/jamaoncol.2025.1916). Its abstract cites the registry id NCT04969887, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2025","url":"https://doi.org/10.1001/jamaoncol.2025.1916"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40608313/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40608313"},{"label":"ClinicalTrials.gov NCT04969887","url":"https://clinicaltrials.gov/study/NCT04969887"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04969887"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2025,"doi":"10.1001/jamaoncol.2025.1916","pmid":"40608313","authors":"Gao B, Carlino MS, Michael M, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04969887 with the most citations, so it is the natural first reading for anyone following the MOST-CIRCUIT trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-nct04969887-jama-oncol-2025/","neighbours":{"trial":[{"id":"nct04969887","kind":"trial","name":"Combination Immunotherapy in Rare Cancers Under InvesTigation","route":"/trials/nct04969887/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}]}}