ROSELLA: A phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG-3073, ENGOT-ov72).

Abstract

LBA5507 Background: Relacorilant is an investigational, oral, selective glucocorticoid receptor antagonist (SGRA) that increases tumor sensitivity to chemotherapy-induced apoptosis. In a phase 2 study, the addition of relacorilant to nab-paclitaxel improved progression-free survival (PFS) and showed a trend towards improved overall survival (OS), with a comparable safety profile to nab-paclitaxel monotherapy, in patients with platinum-resistant ovarian cancer (PROC). The aim of this phase 3 study is to confirm the efficacy and safety of relacorilant + nab-paclitaxel in a larger population. Methods: ROSELLA (NCT05257408) is a randomized, controlled, open-label, global study of relacorilant + nab-paclitaxel compared to nab-paclitaxel monotherapy in patients with PROC. Patients were randomized 1:1 to either relacorilant (150 mg the day before, day of, and day after nab-paclitaxel) + nab-paclitaxel (80 mg/m 2 on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel alone (100 mg/m 2 on the aforementioned schedule). Randomization was stratified by prior lines of therapy and region. Key eligibility criteria included 1–3 prior lines of anticancer therapy and prior bevacizumab. The dual primary endpoints are PFS by blinded independent central review (BICR) and OS. Secondary endpoints include PFS by investigator, objective response rate, best overall response, duration of response, and safety. PFS and OS endpoints were analyzed using Kaplan-Meier methods. A 2-sided stratified log-rank test was used to compare treatment groups. Hazard ratios (HR) were estimated with a Cox regression model. Results: A total of 381 women were randomized, all baseline characteristics were well balanced and 39% had received prior therapy in the PROC setting. ROSELLA met its primary endpoint: Patients receiving relacorilant + nab-paclitaxel had a statistically significant improvement in PFS by BICR compared to nab-paclitaxel monotherapy (HR 0.70, 95% CI 0.54-0.91, median 6.5 v 5.5 months, P=0.008); PFS by investigator showed a consistent benefit (HR 0.71, P=0.003). At an interim analysis, there was a clinically significant improvement in OS with the addition of relacorilant to nab-paclitaxel (HR 0.69, 95% CI 0.52-0.92, median 16.0 v 11.5 months, P=0.01). Adverse events (AEs) were comparable across study arms, relacorilant + nab-paclitaxel was well tolerated with no new safety signals. The most frequently reported AEs were known toxicities of nab-paclitaxel: anemia (58%), neutropenia (56%), and nausea (39%). Conclusion: Relacorilant + nab-paclitaxel is the first treatment regimen to demonstrate a PFS and OS benefit in patients with PROC compared to a weekly taxane, the most efficacious comparator. These positive efficacy data and a favorable safety profile position relacorilant + nab-paclitaxel as a new standard for patients with PROC, without the need for biomarker selection. Clinical trial information: NCT05257408 .