A Comprehensive Review of Relacorilant in the Treatment of Platinum-Resistant Ovarian Cancer

Treating ovarian cancer that has relapsed and developed resistance or lack of response to platinum-based agents is one of the most formidable obstacles in gynecologic oncology, as clinical outcomes remain dismal despite medical advancements. Emerging research indicates that the body's natural corticosteroids can block standard chemotherapy from triggering tumor cell death due to their inherent survival and antiapoptotic signals. This specific protective mechanism appears to be regulated through the glucocorticoid receptor (GR) signaling axis. To counteract this, scientists developed relacorilant (CORT125134), a novel, orally bioavailable selective GR modulator designed to displace cortisol, block its antiapoptotic properties, and restore tumor vulnerability to cytotoxic drugs. This review analyzes the molecular logic behind GR targeting and critically examines clinical data from key three-arm, randomized, controlled, open-label phase II and phase III clinical trials evaluating relacorilant combined with nab-paclitaxel in patients with recurrent, platinum-resistant ovarian malignancies. The initial phase II study compared nab-paclitaxel alone against two distinct scheduling strategies for relacorilant: a daily continuous regimen (100 mg) and an intermittent regimen (150 mg administered the day prior to, the day of, and the day following nab-paclitaxel delivery). Notably, the intermittent dosing arm yielded superior progression-free survival, extended duration of response, and improved overall survival relative to chemotherapy alone, while maintaining an acceptable safety profile. These encouraging clinical endpoints validate GR modulation as a promising therapeutic strategy, justifying the transition to a confirmatory phase III trial utilizing the intermittent schedule.