A First-in-class Glucocorticoid Receptor-targeted Therapy for Gynecologic Cancers
Relacorilant was approved for previously treated ovarian, fallopian tube, and peritoneal cancers.
The U.S. Food and Drug Administration (FDA) has approved relacorilant (Lifyorli) in combination with nab-paclitaxel for the treatment of platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in adult patients who have received one to three prior systemic therapies, including at least one regimen containing bevacizumab (Avastin).
Relacorilant is a first-in-class oral selective glucocorticoid receptor antagonist. It works by binding to the glucocorticoid receptor and preventing its natural ligand, cortisol, from activating it. Cortisol is a stress hormone that regulates inflammation, metabolism, and immune responses through activation of the glucocorticoid receptor. Cancer cells can co-opt this physiological stress response by overexpressing the glucocorticoid receptor to blunt the effects of chemotherapy and promote immune suppression. Relacorilant treatment was designed to prevent immune suppression and enhance the effects of chemotherapy by inhibiting cortisol-induced resistance.
Efficacy of the relacorilant and nab-paclitaxel combination was evaluated in the ROSELLA clinical trial, a multicenter, open-label, phase III study conducted in 381 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. One to three prior lines of systemic therapy were permitted, and previous exposure to bevacizumab was required. Patients were randomly assigned (1:1) to receive relacorilant in combination with nab-paclitaxel or nab-paclitaxel alone.
Median progression-free survival was 6.5 months among patients who received relacorilant in combination with nab-paclitaxel and 5.5 months among those who received nab-paclitaxel alone, corresponding to a 30% decrease in the risk of disease progression or death. Median overall survival was 16 months in the relacorilant and nab-paclitaxel group and 11.9 months in the nab-paclitaxel arm. The overall risk of death in individuals who received the combination treatment was 35% lower compared with those who received nab-paclitaxel alone.
According to the prescribing information, relacorilant in combination with nab-paclitaxel is not indicated for patients who require corticosteroid therapy for a lifesaving indication.
The recommended dosage of nab-paclitaxel is 80 mg/m2 given intravenously on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity occurs. The recommended dosage of relacorilant is 150 mg orally once on the day before, day 1, and day 2 of each nab-paclitaxel treatment cycle until disease progression or unacceptable toxicity occurs.
Cancers of the ovary, fallopian tube, and peritoneum (the membrane that covers the abdominal wall) form in the epithelial cells lining these tissues. Since these cancers arise in the same type of tissue, they are treated similarly. According to federal statistics, it was estimated that 20,890 women would be diagnosed with ovarian cancer and 12,730 would die of the disease in the United States in 2025.
The FDA rendered its decision on March 25, 2026. Check this resource for updated information on all therapeutics regulated by the FDA.