The MOST-CIRCUIT trial showed that combined treatment with nivolumab and ipilimumab achieved a high objective response rate and prolonged progression-free survival in patients with advanced mismatch repair-deficient, microsatellite instability-high noncolorectal cancers. The six-month progression-free survival was 71%, and the treatment was associated with a manageable safety profile with the most common severe adverse events being immune-related.
Study
|
Nonrandomized, multicenter, phase 2 basket trial [MOST-CIRCUIT] |
| Advanced dMMR/MSI-H noncolorectal cancers |
| Nivolumab + Ipilimumab (N=52, Endometrial n=26; GI n=10)
|
Efficacy
|
ORR: 63% |
| 6-mo PFS: 71% |
| mOS: Not reached |
| mPFS: Not reached
|
Safety
|
Grade >=3 AE: immune-related hepatotoxicity (6%), enterocolitis (6%) |
| Treatment discontinuations: 5% for immune-related AEs
|
JAMA Oncol. Published online November 13, 2025.
http://doi.org/10.1001/jamaoncol.2025.4721
Reviewed by Ulas D. Bayraktar, MD on Dec 8, 2025
