# Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial

Source: https://onco.cc/key-papers/paper-nct04969887-jama-oncol-2025/  
OnCo record `paper-nct04969887-jama-oncol-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

Indexed 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: europepmc-ingest
- Journal: JAMA Oncology
- Year: 2025
- DOI: 10.1001/jamaoncol.2025.1916
- Authors: Gao B, Carlino MS, Michael M, et al.
- What it means: 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.

## Sources

- JAMA Oncol 2025: https://doi.org/10.1001/jamaoncol.2025.1916
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40608313/
- Europe PMC: https://europepmc.org/article/MED/40608313
- ClinicalTrials.gov NCT04969887: https://clinicaltrials.gov/study/NCT04969887

## Connected records

- trials: [Combination Immunotherapy in Rare Cancers Under InvesTigation](https://onco.cc/trials/nct04969887/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)

---
JSON: https://onco.cc/api/v1/entities/paper-nct04969887-jama-oncol-2025.json