CHMP has recommended EU marketing authorization for relacorilant combined with nab-paclitaxel in platinum-resistant ovarian cancer.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending that the European Commission (EC) approve relacorilant (Lifyorli) combined with nab-paclitaxel (Abraxane) for adult patients with platinum-resistant ovarian cancer.1
The recommendation is based on data from a phase 2 trial (NCT03776812) and the
Data from ROSELLA which were presented at the
At the primary analysis of the trial, median PFS by blinded independent central review was 6.5 months (95% CI, 5.6-7.4) vs 5.5 months (95% CI, 3.9-5.9), in the relacorilant arm vs the nab-paclitaxel arm (HR, 0.70; 95% CI, 0.54-0.91; P = .0076), respectively.2
“The CHMP’s positive opinion takes us a big step closer to bringing the benefits of glucocorticoid receptor antagonism to patients in the EU,” said Joseph K. Belanoff, MD, chief executive officer of Corcept in a news release.1
The open label, randomized trial enrolled 381 patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer who had an ECOG performance status of 1 or less.2 Patients also needed to have disease progression less than 6 months after their last dose of platinum-based therapy, received 1 to 3 prior lines of therapy, and prior bevacizumab (Avastin) exposure.2
If patients had clinically relevant toxicity from prior systemic therapy or radio therapy that was not reslove to at least grade 1, major surgery within 4 weeks to randomization, progressed within 1 month of their last dose of frontline platinum-containing therapy, or had not received prior bevacizumab, they were not included in the trial.3
Patients were randomly assigned to receive oral relacorilant at 150 mg plus 80 mg/m² of nab-paclitaxel intravenously on days 1, 8, and 15 of each 28-day cycle or to nab-paclitaxel monotherapy at 100 mg/m² on the same schedule, until progression or unmanageable toxicity.2
PFS per RECIST 1.1 criteria and blinded independent central review and OS were the primary end points of the trial. Secondary end points included, PFS per investigator assessment, overall response rate, duration of response, clinical benefit rate, and safety.
Baseline characteristics revealed that median age among patients was 61 years (range, 26-85) and 62 years (range, 33-86), in relacorilant and nab-paclitaxel arms, respectively. Most patients were White in both the relacorilant arm (72.3%) and nab-paclitaxel arm (69.9%) and had an ECOG performance status of 1 or 2 (relacorilant, 28.2%; nab-paclitaxel, 32.6%).
For each respective arm, BRCA1/2 mutations were reported in 12.2% and 12.4% of patients, and primary platinum-refractory disease was reported in 6.9% and 6.7%. All patients in both arms had received prior bevacizumab, with 99.5% in each arm receiving a prior taxane. In the relacorilant arm, 4.3% of patients had received a prior taxane in the platinum-resistant setting compared with 3.6% in the nab-paclitaxel arm.
Among patients with a taxane-free interval of 6 months or less who received relacorilant plus nab-paclitaxel (n = 22), the median OS was 16.7 months (95% CI, 7.9-18.7) vs 11 months (95% CI, 7.6-13.3) for those who received nab-paclitaxel alone (n = 33; HR 0.60; 95% CI, 0.31-1.15). Among those with a taxane-free interval of more than 6 months in the relacorilant arm (n = 165), the median OS was 15.7 months (95% CI, 12.4-19.3) compared with 12.1 months (95% CI, 9.8-14.3) in the nab-paclitaxel arm (n = 159; HR, 0.66; 95% CI, 0.51-0.86).
At 12 and 18 months, OS rates were 60% and 46% with relacorilant plus nab-paclitaxel vs 50% and 27% with nab-paclitaxel alone, respectively.
Among safety-evaluable patients, any-grade adverse effects (AEs) occurred in 100% of patients who received relacorilant plus nab-paclitaxel (n = 188) vs 99.5% of those who received nab-paclitaxel alone (n = 190). Grade 3 or higher AEs occurred in 74.5% vs 59.5% of patients, respectively, and serious AEs occurred in 35.1% vs 23.7%. AEs led to relacorilant discontinuation in 10.1% of patients and to nab-paclitaxel discontinuation in 9.6% in the relacorilant arm vs 7.9% of patients in the monotherapy arm.
