ROSELLA: A phase 3 study of relacorilant in combination with nab-paclitaxel versus investigator’s choice in advanced, platinum-resistant, high-grade epithelial ovarian, primary peritoneal, or fallopian-tube cancer.

TPS5620 Background: Chemotherapy resistance is a major concern in the treatment of advanced platinum-resistant and platinum-refractory ovarian cancer. One mechanism of resistance is driven by cortisol, which can suppress the apoptotic pathways that chemotherapy agents rely upon, eg, suppression of BCL2 and FOXO3a pathways. Preclinical and clinical data indicate that glucocorticoid receptor (GR) antagonism may reverse the anti-apoptotic effects of cortisol, thereby restoring the efficacy of cytotoxic agents. Relacorilant is a selective GR modulator that has shown promise in overcoming resistance when combined with taxanes (particularly nab-paclitaxel) in preclinical models (Greenstein & Hunt 2021) and early-phase clinical studies (Munster et al. 2019) in various solid tumors. A randomized, controlled phase 2 study of relacorilant + nab-paclitaxel found clinically meaningful improvements in progression-free survival (PFS) and duration of response (DOR) without increased side effect burden in patients with recurrent, platinum-refractory and platinum-resistant ovarian cancer (Colombo et al. 2021). The aim of this phase 3 study is to confirm these phase 2 findings in a larger patient population. Methods: ROSELLA (EudraCT 2022-000662-18, NCT pending) is a phase 3, randomized, 2-arm, open-label, multicenter study of relacorilant + nab-paclitaxel compared to investigator’s choice of chemotherapy agents in patients with confirmed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. The trial is being conducted at multiple sites in North America and Europe and has a planned enrollment of 360 patients. Patients are randomized 1:1 to either relacorilant (150 mg the day before, day of, and day after nab-paclitaxel infusion) + nab-paclitaxel (80 mg/m2 on days 1, 8, and 15 of each 28-day cycle) or investigator’s choice of chemotherapy (liposomal doxorubicin, paclitaxel, topotecan, or nab-paclitaxel). Randomization is stratified by prior lines of therapy (1 vs > 1), region of world (North America vs Europe), and prior bevacizumab (yes/no). Adult female patients with platinum-resistant disease (progression within 6 months of completion of platinum-containing therapy), excluding patients with primary platinum refractory disease, who have received 1–3 lines of prior systemic anticancer therapy and at least 1 prior line of platinum therapy are being enrolled. Life expectancy ≥3 months, adequate organ function, and ECOG performance status of 0 or 1 are required. The primary study endpoint is PFS by blinded independent central review. Key secondary endpoints include overall survival, PFS by investigator, overall response rate, best overall response, DOR, clinical benefit rate, safety, quality of life, CA-125, pharmacodynamics, and pharmacokinetics. Clinical trial information: 2022-000662-18.