Nivolumab for mismatch-repair-deficient gynecological cancers: single-center phase 2 trial with biomarker analyses

PD-1 inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. A phase 2 trial at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated nivolumab for dMMR uterine or ovarian cancers. The trial met the co-primary endpoints of objective response rate and progression-free survival rate at 24 weeks. The median overall survival was not reached at median follow-up of 42.1 months, with one-year OS rate 79%. Grade 3 or 4 treatment-related adverse events were observed in 29%; there were no grade 5 TRAEs. Exploratory analyses showed that the presence of dysfunctional or terminally dysfunctional T cells and their interaction with PD-L1⁺ cells were independently associated with PFS24, as was presence of MEGF8 or SETD1B somatic mutations. The authors conclude that the trial met its co-primary endpoints and identified factors associated with response to PD-1 blockade in dMMR cancers.