The final overall survival (OS) analysis of the phase III ROSELLA clinical trial reports an increase of 4.1 months in median OS in patients with platinum-resistant ovarian cancer who received relacorilant in addition to nab-paclitaxel vs those who received nab-paclitaxel alone.
Relacorilant is a first-in-class selective glucocorticoid receptor antagonist that inhibits cortisol survival signals and increases the sensitivity of tumours to several classes of cytotoxic chemotherapy. [Oncotarget 2021;12:1243-1255; Clin Cancer Res 2022;28:3214-3224; J Clin Oncol 2023;41:4779-4789] The addition of relacorilant to nab-paclitaxel was associated with superior progression-free survival vs nab-paclitaxel monotherapy (hazard ratio [HR], 0.70; p=0.0076) in the primary analysis of the international, randomized, controlled, open-label, phase III ROSELLA trial (n=381). [Lancet 2025;405:2205-2216]
The protocol-specified final analysis of OS was conducted at 76 percent of data maturity. The addition of relacorilant to nab-paclitaxel resulted in a statistically significant improvement in OS (HR, 0.65; 95 percent confidence interval [CI], 0.51–0.83; two-sided stratified log-rank p=0.0004). After a median follow-up of 24.8 months, median OS in the relacorilant combination group was extended by 4.1 months compared with nab-paclitaxel alone (16.0 vs 11.9 months). [Lancet 2026;407:1513-1524]
“The Kaplan–Meier curves remain well separated and increasingly divergent throughout the follow-up period, suggesting the addition of relacorilant offers a long-term benefit,” highlighted the investigators.
The addition of relacorilant to nab-paclitaxel improved OS across all prespecified subgroups. All patients had received prior bevacizumab, 44 percent of patients had received three previous lines of therapy, and 61 percent of patients had received a poly(ADP-ribose) polymerase inhibitor. The trial was conducted in 14 countries across Australia, Europe, Latin America, North America, and South Korea. Asian patients represented 13 percent of the overall population.
The investigators emphasized ROSELLA’s all-comer design, which did not require biomarker selection of patients. “Relacorilant selectively antagonizes the glucocorticoid receptor … [which] is expressed by the tumour cells of >95 percent of epithelial ovarian cancers,” they wrote.
Neutropenia (64 percent), anaemia (61 percent), fatigue (54 percent), and nausea (44 percent] were the most common treatment-emergent adverse events (AEs) in the relacorilant combination group. The overall frequencies of grade ≥3 AEs (75 vs 59 percent), all serious AEs (35 vs 24 percent), and grade ≥3 neutropenia (44 vs 25 percent), anaemia (18 vs 9 percent), and fatigue (9 vs 2 percent) were numerically higher in the combination group. However, the investigators pointed out that the combination group had a 30 percent longer median treatment duration with nab-paclitaxel compared with the nab-paclitaxel monotherapy group (4.52 vs 3.48 months). The rates of grade ≥3 neutropenia and anaemia were similar between groups following adjustment for the duration of study drug treatment.
Analysis of patient-reported data on multiple outcomes showed that only two items reached the minimally important difference threshold between the two treatment arms, favouring the nab-paclitaxel monotherapy group – namely, nausea and vomiting (p=0.0007) and appetite loss (p=0.0009).
“Combined with the evidence from previous studies, the positive OS data support relacorilant plus nab-paclitaxel as a potential new standard treatment option for patients with platinum-resistant ovarian cancer, without the need for biomarker selection,” concluded the researchers.