Relacorilant Combo Significantly Improves Survival in Platinum-Resistant Ovarian Cancer
New combination therapy of relacorilant and nab-paclitaxel shows promise in extending survival for patients with platinum-resistant ovarian cancer.
Ovarian cancer: ©Dr_Microbe - stock.adobe.com
A significant advance in the management of platinum-resistant ovarian cancer (PROC) was unveiled at the ESMO Gynecological Cancers Congress 2025, where results from the phase 3 ROSELLA trial (NCT05257408) demonstrated that the addition of relacorilant to nab-paclitaxel significantly prolonged progression-free survival (PFS) and showed a promising trend in overall survival (OS) compared with nab-paclitaxel monotherapy. These findings offer a new therapeutic avenue for patients facing this challenging disease, for whom treatment options remain limited.1,2
The ROSELLA trial enrolled 381 patients with ovarian cancer who had experienced disease progression within 6 months of their last platinum-based therapy. The primary end point, PFS assessed by blinded independent central review (BICR), was significantly improved in the combination arm, with a hazard ratio (HR) of 0.70 (95% CI, 0.54-0.91; log-rank P =.0076). Specifically, the median PFS via BICR was 6.54 months (95% CI, 5.55-7.43) with relacorilant and nab-paclitaxel (n = 188) vs 5.52 months (95% CI, 3.94-5.88) with nab-paclitaxel alone (n = 193). This translates to a near doubling in the proportion of patients without progression at 12 months in the relacorilant plus nab-paclitaxel group (25%) vs the nab-paclitaxel monotherapy group (13%), highlighting a clinically meaningful benefit.
Interim analysis of OS, with approximately 50% maturity, further supported these positive outcomes, revealing a clinically meaningful improvement in OS with the combination therapy (HR 0.69; 95% CI 0.52-0.92; nominal P =.0121). The median OS was 15.97 months (95% CI, 13.47-not reached [NR]) with relacorilant vs 11.50 months (95% CI, 10.02-13.57) with nab-paclitaxel alone. These early OS data are particularly encouraging in a patient population known for poor prognosis and limited long-term survival.
An exploratory analysis delved into prognostic subgroups, consistently demonstrating the benefit of relacorilant plus nab-paclitaxel, even in those with particularly poor prognoses. In 112 patients with a primary platinum-free interval of 6 months or less, the combination therapy yielded a PFS HR of 0.50 (95% CI, 0.30-0.84) and an interim OS HR of 0.52 (95% CI, 0.31-0.89). This consistent benefit across challenging subgroups underscores the broad potential applicability of this regimen.
The rationale behind combining relacorilant with nab-paclitaxel is rooted in overcoming chemotherapy resistance.
“Activation of the glucocorticoid pathway has been shown to reduce the efficacy of chemotherapy by inhibiting drug-induced apoptosis,” explained Robert L. Coleman, MD, gynecologic oncologist at Texas Oncology, in his commentary during the congress.2 “Preclinical experiments and limited clinical data suggested that blocking the GR with agents such as relacorilant could mitigate this effect, potentiating cytotoxicity in breast and ovarian cancer models. Weekly nab-paclitaxel was developed to avoid some of the common taxane toxicities, including hypersensitivity reactions and gastrointestinal symptoms—adverse effects commonly treated with steroid premedication. This enabled the hypothesis that combining these two factors, GR regulation by relacorilant and a steroid-free taxane (nab-paclitaxel), could lead to better efficacy in patients with ovarian cancer.”
Regarding safety and tolerability, grade ≥3 treatment-emergent adverse events were reported in 74.5% of patients receiving relacorilant plus nab-paclitaxel compared with 59.5% in the nab-paclitaxel monotherapy arm. However, when adjusted for the longer duration of exposure observed with the combination therapy, the safety profile appeared broadly similar between the 2 groups. This suggests that the addition of relacorilant did not introduce significant additional toxicity, maintaining a manageable safety profile despite the extended treatment duration and improved efficacy.
These findings position relacorilant in combination with nab-paclitaxel as a compelling new option for patients with platinum-resistant ovarian cancer. While acknowledging the inherent hazards of cross-trial comparisons, Coleman noted that the ROSELLA trial outcomes compare favorably with those seen in the MIRASOL trial (NCT04209855), which evaluated mirvetuximab soravtansine (Elahere) in a biomarker-selected, FRα-positive platinum-resistant ovarian cancer population—notably the first agent to demonstrate an OS improvement in this difficult-to-treat setting.
The ongoing KEYNOTE-B96 trial (NCT05116189), investigating pembrolizumab (Keytruda) in combination with paclitaxel with or without bevacizumab (Avastin) in platinum-resistant recurrent ovarian cancer, is also anticipated to provide further insights into optimizing treatment strategies. The collective results from MIRASOL, ROSELLA, and KEYNOTE-B96 will be instrumental in informing future regimens, sequencing strategies, and personalized treatment approaches for diverse subpopulations of patients with platinum-resistant ovarian cancer.2
