Glucocorticoid receptor antagonist bypasses platinum resistance in ovarian cancer

Relacorilant, a selective glucocorticoid receptor (GR) antagonist, improves the survival of participants with platinum-resistant ovarian cancer by restoring their sensitivity to chemotherapy, as demonstrated by the results from the phase 3 ROSELLA trial.

The prognosis for patients with platinum-resistant ovarian cancer is poor, and new treatment options are needed. GR signalling is a key player in chemotherapy resistance [1]. Relacorilant is a selective GR antagonist that, when combined with nab-paclitaxel chemotherapy, demonstrated clinical efficacy in participants with platinum-resistant ovarian cancer in an open-label phase 2 trial (NCT03776812) [2]. The phase 3 ROSELLA trial (NCT05257408), presented by Prof. Alexander Olawaiye (University of Pittsburgh Medical Center, PA, USA), further explored the efficacy and safety of relacorilant [3].

A total of 381 participants with platinum-resistant ovarian cancer were 1:1 randomised to the relacorilant-nab-paclitaxel combination or nab-paclitaxel alone until progression or unmanageable toxicity. The primary endpoints were progression-free survival (PFS) and overall survival (OS); key secondary endpoints included objective response rate and safety.

After a median follow-up of 9 months, median PFS was in favour of the combination arm with 6.54 months (95% CI 5.55–7.73) compared to 5.52 months (95% CI 3.94–5.88) in the chemotherapy alone arm (HR 0.70; 95% CI 0.54–0.91; P=0.0076; see Figure). Although not yet mature (50%), the median OS also favoured the combination arm, reaching 15.97 months (95% CI 13.47 to not reached) versus 11.50 months (95% CI 10.02–13.57; HR 0.69; 95% CI 0.52–0.92; P=0.0121).

Figure: Relacorilant significantly improved progression-free survival in participants with platinum-resistant ovarian cancer assessed by blinded review [3]



CI, confidence interval; HR, hazard ratio; m, median; PFS, progression-free survival.

The objective response rate was improved by 6.8% (36.9% vs 30.1%) in the combination arm, and ascites was less common in participants who received relacorilant (5% vs 11%).  The incidence of grade ≥3 treatment-emerging adverse events was increased in the combination arm (74.5% vs 59.5%).

“Relacorilant plus nab-paclitaxel offers an efficacious treatment regimen for women with platinum-resistant ovarian cancer, without the need for a biomarker”, concluded Prof. Olawaiye.

1. Greenstein AE, et al. Oncotarget 2021;12:1243–1255.
2. Colombo N, et al. J Clin Oncol. 2023;41(30):4779–4789.
3. Olawaiye A, et al. 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, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.

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Posted on 30 July 2025