Domenica Lorusso, MD, PhD
The addition of nab-paclitaxel to relacorilant (Abraxane) further improved progression-free survival (PFS) vs nab-paclitaxel alone in patients with platinum-resistant ovarian cancer, meeting the primary end point of the phase 3 ROSELLA trial (NCT05257408) and demonstrating the potential for this combination to improve upon the current standard of care (SOC), according to Domenica Lorusso, MD, PhD.1
Data from the study, which were previously presented at both the 2025 ASCO Annual Meeting and the 2025 ESMO Gynecological Cancers Congress, revealed that the median PFS in the overall population was 6.54 months (95% CI, 5.55-7.43) and 5.52 months (95% CI, 3.94-5.88) with relacorilant plus nab-paclitaxel (n = 188) vs nab-paclitaxel (n = 193), respectively (HR, 0.70; 95% CI, 0.54-0.91; P = .0076). At 6 months, the respective PFS rates were 52% vs 42%. At 12 months, respective PFS rates were 25% vs 13%.
“More than 60% of these patients had [previously] received PARP inhibitors,” Lorusso explained during an interview with OncLive®. “We know that these patients are very difficult to treat, as [many] of these patients are [not only] resistant to PARP [inhibitors], but are also resistant to platinum[-based chemotherapy]. It’s a huge unmet clinical need to identify treatments that are effective for patients progressing during PARP [inhibitor therapy].”
In the interview, Lorusso discussed the background of the ROSELLA trial, efficacy and safety data from the study, potential clinical implications, and next steps for evaluating the relacorilant-based regimen.
Lorusso is the director of the Gynecological Oncology Unit at Humanitas Hospital San Pio X in Milan, as well as a full professor of Obstetrics and Gynecology at Humanitas University in Rozzano, Italy.
OncLive: What was the rationale and design of the ROSELLA trial?
Lorusso: We have discovered that glucocorticoid receptor signaling can reduce sensitivity to chemotherapy. Preclinical and early clinical data suggest that ovarian cancer expresses the glucocorticoid receptor, which is a marker of poor prognosis. The data suggest that when cortisol activates the glucocorticoid receptor, it can induce the transcription of anti-apoptotic genes that are involved in epithelial-mesenchymal transition and resistance to chemotherapy. This is why targeting this receptor with relacorilant, a selective glucocorticoid receptor antagonist, is interesting. We have phase 2 data suggesting that when we combine intermittent relacorilant with nab-paclitaxel, we can increase PFS and overall survival [OS] in platinum-resistant ovarian cancer. We chose nab-paclitaxel instead of weekly paclitaxel, which is more commonly used in ovarian cancer because nab-paclitaxel does not require corticosteroid premedication. Because relacorilant is a glucocorticoid receptor antagonist, we only combine drugs that do not require a glucocorticoid receptor.
The ROSELLA trial is a randomized phase 3 trial comparing nab-paclitaxel with relacorilant plus nab-paclitaxel in platinum-resistant and refractory patients, [which we defined as] patients [whose disease] progressed between 1 and 3 months [after] prior platinum[-based therapy]. We are analyzing the data of the efficacy of the drug in patients progressing during PARP [inhibitor therapy]. These patients could not have received more than 3 prior lines of therapy, and prior bevacizumab [Avastin] was required. The trial has 2 primary end points: PFS, as evaluated according to RECIST 1.1 criteria by a blinded independent central review, and OS.
What were the key efficacy data?
The trial met its primary [PFS] end point, [with] a significant increase in PFS reported in patients treated with relacorilant/nab-paclitaxel. The median PFS was 5.5 months with nab-paclitaxel vs 6.5 months with relacorilant plus nab-paclitaxel. The HR was 0.70, suggesting a 30% reduction in the risk of [disease] progression [or death]. [Data from] the interim analysis for OS [showed that] the median OS increased from 11.5 months in the nab-paclitaxel arm to 15.97 months in the relacorilant plus nab-paclitaxel arm, with a HR of 0.69. [These data are] not yet mature; we have to wait for the final OS data.
Interestingly, there was a slight improvement in overall response rate [ORR], [with a] 7% improvement. [The ORR was] 30.1% with nab-paclitaxel and 36.9% with relacorilant plus nab-paclitaxel. [Regarding] the clinical benefit rate, there was a 12% [improvement with the relacorilant combination].
What was the safety profile of relacorilant in this study?
The safety profile of the drug was manageable. The most frequently reported adverse effects [AEs] were neutropenia, anemia, and fatigue in patients treated with the relacorilant plus nab-paclitaxel arm. Hematologic AEs included neutropenia and anemia. [Interestingly], the duration of exposure was different in patients receiving nab-paclitaxel or nab-paclitaxel plus relacorilant. When we adjusted the hematological toxicity of neutropenia and anemia for the duration of exposure, the incidence and rates of neutropenia and anemia were very comparable between the 2 treatment arms. We can conclude that the toxicity profile is mainly hematological, but manageable.
What are the potential clinical implications of these findings?
[Nab-paclitaxel plus relacorilant] can be easily considered a new SOC for our patient with platinum-resistant and refractory ovarian cancer. [What was interesting about] the trial is that the comparator arm was nab-paclitaxel. According to the indirect trial comparison data we have, [this is] as effective as weekly paclitaxel, [which] we consider [to be] the most effective drug in the platinum-resistant setting. What we demonstrate with the ROSELLA trial is that when we add relacorilant to the best drug in the platinum-resistant setting, we further increase PFS.
What future investigations are planned based on this research?
We are now running the BELLA trial [NCT06906341], which is a single-arm phase 2 trial combining nab-paclitaxel and relacorilant with bevacizumab. In the ROSELLA trial, all the patients should have received prior bevacizumab; therefore, we only have the data of nab-paclitaxel plus relacorilant. In the BELLA trial, we have both cohorts: the patients who have previously received bevacizumab, and patients who have not previously received bevacizumab. All these patients are treated with the triplet regimen of nab-paclitaxel, relacorilant, and bevacizumab.
Reference
Lorusso D, Gladieff L, Gilbert L, et al. Phase III results of relacorilant + nab-paclitaxel vs nab-paclitaxel in platinum-resistant ovarian cancer (PROC) (ROSELLA, GOG-3073, ENGOT-ov72): secondary endpoints. Ann Oncol. 2025;10(suppl 5):105332. doi:10.1016/j.esmoop.2025.105332