On March 25, the U.S. Food and Drug Administration (FDA) approved relacorilant (Lifyorli), a glucocorticoid receptor antagonist, in combination with nab-paclitaxel for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab.
ROSELLA Trial
Efficacy was evaluated in ROSELLA (ClinicalTrials.gov identifier NCT05257408), a multicenter, open-label trial which included 381 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were permitted to receive up to three prior lines of systemic therapy, and prior receipt bevacizumab was required for enrollment. The trial excluded patients who required chronic or frequent use of glucocorticoids.
Patients were randomly assigned 1:1 to receive relacorilant in combination with nab-paclitaxel or nab-paclitaxel alone. The major efficacy outcome measures were progression-free survival assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival. Median progression-free survival was 6.5 months (95% confidence interval [CI] = 5.6–7.4 months) in the relacorilant/nab-paclitaxel arm and 5.5 months (95% CI = 3.9–5.9 months) in the nab-paclitaxel alone arm (hazard ratio [HR] = 0.70, 95% CI = 0.54–0.91, two-sided P = .0076). Median overall survival was 16 months (95% CI = 13–18.3 months) in the relacorilant/nab-paclitaxel arm and 11.9 months (95% CI = 10–13.8 months) in the nab-paclitaxel arm (HR = 0.65, 95% CI = 0.51–0.83, two-sided P = .0004).
The prescribing information includes a contraindication for patients who require corticosteroids for a lifesaving indication as well as warnings and precautions for neutropenia and severe infections, adrenal insufficiency, exacerbation of conditions treated with glucocorticoids, and embryo-fetal toxicity. The most common adverse reactions (incidence ≥ 20%), including laboratory abnormalities, that occurred in patients treated with relacorilant in combination with nab-paclitaxel were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite.
Recommended Dosage
The recommended dosage of relacorilant is 150 mg orally once on the day before, the day of, and the day after each nab-paclitaxel infusion until disease progression or unacceptable toxicity. The recommended dosage for nab-paclitaxel is 80 mg/m2 administered as an intravenous infusion on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the Applicant to facilitate the FDA’s assessment. The FDA approved this application 2.5 months ahead of the FDA goal date.
