Dr Lorusso on the Rationale for Investigating Relacorilant Plus Nab-Paclitaxel 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.”

Domenica Lorusso, MD, PhD, the director of Gynaecological Oncology Unit at Humanitas Hospital San Pio X, and a full professor of Obstetrics and Gynaecology at Humanitas University, explained the impetus for evaluating relacorilant plus nab-paclitaxel (Abraxane) for the treatment of patients with platinum-resistant ovarian cancer in the phase 3 ROSELLA trial (NCT05257408).

Data from preclinical and early clinical studies have shown that ovarian cancer expresses the glucocorticoid receptor, which has been shown to lead to a poorer prognosis, Lorusso began. Data have shown that the glucocorticoid receptor signaling could potentially reduce sensitivity to chemotherapy, she explained. Additionally, data demonstrated that when cortisol activates the glucocorticoid receptor, it can induce the transcription of anti-apoptotic genes associated with epithelial-mesenchymal transition and resistance to chemotherapy, she added. The rationale of the ROSELLA study was to target the respective receptor with relacorilant, she emphasized.

Furthermore, prior phase 2 data revealed that the combination of relacorilant and nab-paclitaxel led to improved progression-free survival (PFS) and overall survival (OS) in patients with platinum-resistant ovarian cancer, Lorusso continued. When planning for the design of the study, investigators selected nab-paclitaxel instead of weekly paclitaxel, although paclitaxel is a commonly used chemotherapy in ovarian cancer, she stated. Lorusso noted that nab-paclitaxel does not require corticosteroid premedication, and relacorilant is a glucocorticoid receptor antagonist; therefore, the drugs were chosen because they do not require a glucocorticoid receptor, she asserted.

In particular, the ROSELLA study evaluated nab-paclitaxel plus relacorilant vs nab-paclitaxel alone in patients with platinum-resistant and refractory ovarian cancer, who experienced disease progression between 1 and 3 months after previously receiving platinum-based therapy, Lorusso contextualized. Of note, the study evaluated the efficacy and safety of relacorilant in patients who had disease progression on a PARP inhibitor, who must have previously been treated with bevacizumab (Avastin), and could not have received more than 3 prior lines of therapy, she clarified. PFS per RECIST 1.1 criteria by blinded independent central review and OS served as the dual primary end point of the study, she concluded.