A Phase 2 trial found that administering the GR antagonist relacorilant intermittently (day before, of, and after chemo) was less toxic than continuous daily dosing. This intermittent schedule showed fewer grade 3 adverse events but still delivered significant improvements in progression-free and overall survival, informing the successful Phase 3 study design.
The addition of relacorilant to nab-paclitaxel offers a new standard of care for platinum-resistant ovarian cancer that benefits a broad patient population. Unlike many modern targeted therapies, its efficacy does not depend on a specific biomarker, simplifying patient selection and broadening its applicability in clinical practice.
Relacorilant's mechanism is not to kill cancer cells directly, but to make chemotherapy more effective. It selectively blocks the glucocorticoid receptor (GR), preventing cortisol from activating anti-apoptotic pathways. This reverses a key survival signal used by cancer cells, thereby restoring the tumor's sensitivity to cytotoxic agents like nab-paclitaxel.
A patient in the BELLA trial with recurrent grade 3 neutropenia avoided treatment discontinuation through dose modification. By skipping the day 8 dose and switching to a day 1 and 15 every 28-day schedule, the patient could tolerate and continue the beneficial therapy, showcasing a practical clinical strategy for managing severe toxicity.
A case study from the ROSELA trial demonstrates that the relacorilant regimen can induce profound and lasting responses. A patient with difficult-to-treat platinum-resistant disease achieved a complete response that was maintained for 22 cycles and persisted even after treatment cessation, a rare and clinically significant outcome for this patient population.
Researchers identified a specific patient subgroup in a Phase 2 trial (1-3 prior therapies including bevacizumab) that showed a markedly stronger overall survival benefit from relacorilant. This key insight led to selecting this exact population for the pivotal Phase 3 ROSELA study, which ultimately met its primary endpoints.