In this interview, David O’Malley, MD, from The Ohio State University’s James Comprehensive Cancer Center, shares insights from the landmark ROSELLA trial. He shares the promising results of relacorilant in combination with nab-paclitaxel for patients with platinum-resistant ovarian cancer, highlighting key efficacy outcomes, clinical implications, and what the future holds for this novel treatment approach.

David O’Malley, MD: I'm Dr David O'Malley from The Ohio State University and the James Comprehensive Cancer Center. I serve as the director and professor within the Division of Gynecological Oncology in the Department of OB/GYN. I'm honored to lead the Division of Gynecological Oncology, as well as our gynecologic oncology phase I program. Nationally, I also lead the ovarian cancer portfolio for Gynecologic Oncology Group (GOG) Partners, a collaborative group under the umbrella of the GOG Foundation.

Can you briefly summarize your study and its key takeaways?

Dr O’Malley: The study evaluated relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer. This was a phase 3, randomized, controlled, open-label trial, known as the ROSELLA trial. It focused on patients with platinum-resistant ovarian cancer who had received 1 to 3 prior therapies and were randomized to receive either nab-paclitaxel alone or nab-paclitaxel with relacorilant.

The trial had dual primary endpoints: progression-free survival (PFS) and overall survival (OS). It met its primary endpoint of PFS with a hazard ratio of 0.7. At interim analysis, there was a meaningful difference in OS, with a hazard ratio of 0.69, translating to a 31% improvement and a four-and-a-half-month improvement in median PFS. It’s important to understand that median values often underestimate the true impact. If one looks at the Kaplan-Meier curves for the survival curves, you see clear differentiation between both the PFS and OS curves.

Regarding toxicity, there were no new signals. The combination's toxicity was very similar to that of single-agent nab-paclitaxel.

How might the relacorilant with nab-paclitaxel combination change the current treatment approach for patients with platinum-resistant ovarian cancer who've progressed after bevacizumab and PARP inhibitors?

Dr O’Malley: These findings represent the first trial to show an OS benefit using weekly taxanes in patients with platinum-resistant ovarian cancer who had progressed after therapies such as bevacizumab and PARP inhibitors. There are also some data suggesting that prior treatment with PARP inhibitors may contribute to a poorer prognosis, further highlighting the importance of this study.

We chose nab-paclitaxel to minimize or eliminate the need for steroids, which aligns well with the mechanism of action of relacorilant. We've always known that weekly taxanes were among the most effective regimens for treating platinum-resistant ovarian cancer. Now, for the first time, we've shown an OS benefit when combining them with relacorilant. This marks a significant impact on the treatment landscape for this difficult-to-treat patient population.

What do the consistent results across poor-prognosis subgroups mean for clinical practice?

Dr O’Malley: Relacorilant, a first-in-class oral selective glucocorticoid receptor antagonist, showed consistent improvement across all subgroups. This consistency suggests that the combination therapy benefits all patients with platinum-resistant ovarian cancer, including the most difficult-to-treat populations, such as those previously treated with bevacizumab.

Were there notable quality-of-life benefits, such as reduced ascites, with relacorilant?

Dr O’Malley: Quality of life will be reported in a separate publication. However, we observed no detriment with the combination compared to single-agent nab-paclitaxel. Full quality-of-life findings will be presented in an upcoming manuscript.

What’s next for relacorilant—are regulatory filings or biomarker studies planned?

Dr O’Malley: The company has indicated that they plan to file soon with both US and European regulators. With the demonstrated improvements in PFS and OS, the final analysis of OS will be reported. We’ll also continue evaluating relacorilant in new combinations. For example, the BELLA trial is investigating a triplet combination of nab-paclitaxel, relacorilant, and bevacizumab. This could offer further benefits in the future, though that trial is still ongoing.

Is there anything else you’d like to add?

Dr O’Malley: It’s exciting that this group of patients did not require a biomarker to demonstrate improvement. The broader applicability of this combination opens up many possibilities for further treatment combinations. This trial represents a significant milestone in treating platinum-resistant ovarian cancer, demonstrating an OS improvement in this challenging population.