As treatment sequencing in ovarian cancer (OC) continues to evolve, an increasing proportion of patients acquire platinum-resistance following frontline poly(ADP-ribose) polymerase (PARP) inhibitor maintenance. These patients often develop cross-resistance to subsequent chemotherapy, with standard single-agent taxanes or pegylated liposomal doxorubicin producing modest and short-lived benefit. The challenge of managing post-PARP disease has demonstrated the need for new therapeutic strategies to restore chemotherapy responsiveness. At the European Society for Medical Oncology (ESMO) Congress, held October 17–21, 2025, investigators presented new subgroup data from the Phase III ROSELLA trial, focusing specifically on patients with platinum-resistant ovarian cancer (PROC) who had prior PARP inhibitor (PARPi) exposure. These results build upon primary findings first reported at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which established Corcept Therapeutics’ relacorilant, a selective glucocorticoid receptor antagonist (SGRA), as a potential first-in-class chemo-sensitizer enhancing cytotoxic efficacy without additional toxicity.
Relacorilant inhibits glucocorticoid receptor (GR) activation by endogenous cortisol which drives transcription of anti-apoptotic genes that allow tumour cells to evade chemotherapy-induced cell death. By blocking this pathway, relacorilant re-sensitizes tumour cells to agents such as nab-paclitaxel. This cortisol-driven resistance modulation represents a biologically novel and biomarker-agnostic mechanism distinct from immune checkpoint or DNA repair inhibition, offering a new approach to overcoming chemoresistance across solid tumours.
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As per the presentation, efficacy was achieved in the PARP-exposed subgroup, with hazard ratios for progression-free survival (PFS) and overall survival (OS) remaining consistent with the overall trial population. PFS assessed by blinded independent central review showed a notable advantage for the relacorilant combination. In the intention-to-treat (ITT) group, the median PFS was 6.5 months for the combination versus 5.5 months for nab-paclitaxel alone, corresponding to a hazard ratio (HR) of 0.70 (95% CI: 0.54–0.91; P=0.0076). In patients with prior PARPi exposure, median PFS was 7.4 months versus 4.6 months, respectively, with a stronger effect size (HR 0.60; 95% CI: 0.42–0.85; nominal P=0.0035). At interim analysis for OS, the combination also trended toward improved outcomes. In the ITT population, median OS was 16.0 months with relacorilant plus nab-paclitaxel and 11.5 months with nab-paclitaxel alone (HR 0.69; 95% CI: 0.52–0.92; P=0.0121). Among prior PARPi-treated patients, OS was similar between groups, with it being 15.6 months versus 12.6 months (HR 0.77; 95% CI: 0.53–1.13; nominal P=0.1834).
The 12-month OS rate was 60% versus 49%, with benefits extending to challenging subgroups, such as primary platinum-refractory and short platinum-free interval (PFI 1-6 months) patients. The combination was well tolerated, with adverse events consistent with nab-paclitaxel monotherapy.
The decision to highlight the PARP-exposed subgroup reflects a significant unmet need, as most recurrent OC cases arise in patients previously treated with PARP inhibitors. Demonstrating consistent efficacy in this population provides validation of relacorilant’s chemo-sensitizing mechanism and supports its potential beyond PARP-naïve populations. These results position relacorilant as one of the few agents showing potential in this heavily pretreated and clinically resistant setting. In GlobalData’s Ovarian Cancer: Opportunity Assessment and Forecast report, key opinion leaders expressed great interest in relacorilant and echoed its impact to re-sensitize tumours to platinum-based chemotherapy, potentially prolonging the duration of benefit from standard-of-care treatment. Additionally, relacorilant has exhibited activity independent of tumour GR expression suggesting its potential applicability across a wide patient population including those lacking established OC biomarkers such as folate receptor-alpha (FRα).
Relacorilant could establish a niche in the post-PARP, platinum-resistant segment, competing with taxane backbones and FRα-directed therapies. Although the subgroup analysis may be underpowered and warrants confirmation in larger multicentre cohorts, relacorilant’s oral dosing, chemo-sensitization ability, biomarker-agnostic efficacy, and safety profile position it well for broad clinical integration. According to GlobalData’s analyst consensus forecast, relacorilant could achieve global sales of $1.9bn by 2031, driven by its role in post-PARP settings and potential expansion to other chemotherapy-resistant malignancies.
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