KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy of intermittently dosed relacorilant in combination with NP for improving OS in platinum-resistant OC patients.
- The primary endpoint was to determine PFS, and the secondary endpoint was OS.
- Researchers noticed improved survival with relacorilant + NP in platinum-resistant OC patients; further investigation in the phase 3 ROSELLA trial is ongoing.
In the context of limited treatment options for advanced, platinum-resistant ovarian cancer (OC), physiologic cortisol levels have been implicated in chemotherapy resistance and tumor progression via apoptosis suppression. Relacorilant, a selective glucocorticoid receptor modulator, has demonstrated promise in preclinical and early clinical trials by restoring chemosensitivity.
Nicoletta Colombo and her team revealed that intermittently dosed relacorilant with nab-paclitaxel (NP) improved progression-free survival (PFS), response duration, and overall survival (OS) compared to NP alone (Colombo et al. J Clin Oncol 2023). Following study closure of this trial, they presented final OS outcomes for relacorilant + NP versus NP monotherapy.
They performed an inclusive analysis, enrolling 178 women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma, who had undergone up to 4 prior chemotherapeutic regimens. The open-label, phase 2 study randomized patients 1:1:1 to (1) NP (80 mg/m2) + intermittent relacorilant (150 mg on the day before, of, and after NP); (2) NP (80 mg/m2) + continuous relacorilant (100 mg QD); or (3) NP monotherapy (100 mg/m2).
NP was administered on days 1, 8, and 15 of each 28-day cycle. PFS was the primary endpoint, with OS as a key secondary endpoint. The focus of this abstract is the comparison between intermittent relacorilant and NP monotherapy arms, which are the treatment regimens under evaluation in the confirmatory phase 3 ROSELLA trial (NCT05257408).
After a median follow-up of 38 months, the median OS was 13.9 months (95% CI: 11.1–18.4) for intermittent relacorilant + NP and 12.2 months (7.7–15.3) for NP monotherapy (HR: 0.69 [95% CI: 0.46–1.02]). Kaplan-Meier estimates of OS were 29.4% (95% CI: 17.7–42.1) and 14.1% (6.6–24.3) at 24 months, and 9.8% (3.6–19.7) and 5.3% (1.4–13.2) at 36 months in the intermittent relacorilant + NP and NP monotherapy arms, respectively.
In the subgroup population similar to that being enrolled in the ROSELLA study (patients with 1–3 prior therapies, including prior bevacizumab, without primary platinum-refractory disease), median OS was 17.9 months (95% CI: 11.9–23.1) for intermittent relacorilant (n=26) + NP and 12.6 months (6.4–15.3) for NP monotherapy (n=31). The safety profile remained consistent with few event differences between the 2 arms in the final analysis.
The study concluded that with an additional approximately 16 months of follow-up, the findings from the primary OS analysis were confirmed. Patients receiving relacorilant + NP experienced a doubled chance of survival at 24 months compared to those receiving NP alone, with no added safety burden. These promising results have paved the way for the currently accruing phase 3 ROSELLA trial.
The trial was sponsored by the Corcept Therapeutics
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=429106&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT03776812
Colombo N, Matulonis U.A., Oaknin A, et al. (2024). “Final overall survival data from a randomized, open-label, phase II study of relacorilant, a selective glucocorticoid receptor modulator, in combination with nab-paclitaxel among patients with recurrent platinum-resistant ovarian cancer.” Presented at SGO 2024.
