Dr Olawaiye Explains Expanding Options in Platinum-Resistant Ovarian Cancer

Platinum-resistant ovarian cancer remains a difficult-to-treat disease with historically limited treatment options and modest survival outcomes. Earlier this year the FDA approved the glucocorticoid receptor antagonist relacorilant (Lifyorli) for use in combination with nab-paclitaxel as an important new addition to the to the treatment paradigm in this setting.¹ 

This approval was supported by findings from the phase 3 ROSELLA trial, in which  at relacorilant plus nab-paclitaxel reduced the risk of death by 35% vs nab-paclitaxel alone (HR, 0.65; 95% CI: 0.51- 0.83; P = .0004). The median overall survival (OS) was 16.0 months vs 11.9 months respectively. The median progression-free survival was 6.5 months vs 5.5 months, respectively (HR,  0.70; 95% CI, 0.54, 0.91; P = .0076).²

At a median follow-up of approximately 25 months, the benefit was consistent across key subgroups, including patients with prior PARP inhibitor exposure and those with multiple prior lines of therapy. Importantly, the trial also showed no requirement for biomarker selection, supporting broader applicability of the novel regimen.² 

Regarding safety, the most common all-grade adverse events in the relacorilant combination group were neutropenia (64%), anemia (61%), fatigue (54%), and nausea (44%).² 

In an interview with Targeted Oncology, Alexander B. Olawaiye, MD discussed  the clinical significance of the OS improvement, how these findings may reshape the platinum-resistant paradigm, and the potential for additional combination approaches with relacorilant.

Targeted Oncology: Given the OS benefit observed in the ROSELLA trial, how do you envision this regimen being integrated into the current treatment landscape for platinum-resistant ovarian cancer?

Dr Alexander Olawaiye: It’s a good problem to have. Just a few years ago, in this group of patients, we had very little to offer. Now we are in a position where we are thinking about sequencing therapies, which reflects the availability of multiple options.

We are in the era of precision medicine, so treatment decisions are often guided by biomarkers such as folate receptor alpha, HER2 expression, and increasingly PD-L1. What makes this regimen unique, however, is that it does not require biomarker selection. Folate receptor alpha is expressed in over 95% of ovarian cancers, so this approach has broad applicability.

Ultimately, I prioritize efficacy when selecting treatment, and this regimen demonstrated strong activity across lines of therapy.

Were there any patient populations in the trial where you would hesitate to use this regimen?

One of the encouraging aspects of this trial was how well tolerated the regimen was. We did not observe specific side effects attributable to the relacorilant component. Most toxicities were consistent with what we expect from nab-paclitaxel.

From a clinical standpoint, if a patient is eligible for nab-paclitaxel, they are likely a suitable candidate for this regimen. For example, because both drugs are metabolized in the liver, even patients with renal challenges may still be considered.

The trial demonstrated a 35% reduction in risk of death and a median OS improvement of 4.1 months. How should clinicians interpret this magnitude of benefit?

This is very exciting because it is only the third trial ever to demonstrate an OS benefit in platinum-resistant ovarian cancer. The hazard ratio of 0.65 is particularly meaningful, as it reflects the relative benefit across the study population.

When you look at the survival curves, by 18 months, nearly half of the patients receiving the regimen were still alive. Historically, many of these patients would not reach 1 year. That level of durability, combined with tolerability, is very encouraging.

Relacorilant targets the glucocorticoid receptor pathway, which is relatively novel in oncology. How does this mechanism support future development?

This is a first-in-class agent, and its mechanism is particularly interesting. Glucocorticoid receptor signaling is associated with poor prognosis because it enables cancer cells to resist chemotherapy.

By inhibiting this pathway, relacorilant restores chemotherapy sensitivity. That’s why it works synergistically with nab-paclitaxel.

Importantly, this mechanism is not limited to one combination. There is strong rationale to combine this approach with other therapies, including antiangiogenic agents, immunotherapies, and even antibody-drug conjugates.

What ongoing research is building on the ROSELLA findings?

The phase 2 BELLA trial (NCT06906341) is evaluating this regimen in combination with bevacizumab (Avastin), and enrollment has already been completed.³ We are awaiting those results.

In addition, the trial has expanded to include patients with platinum-sensitive ovarian cancer and endometrial cancer. There is also interest in exploring combinations with immunotherapy, particularly in tumor types where immune agents have already shown activity.

The possibilities for further development are extensive, and future studies will help determine the most effective strategies.

Are there any additional practical considerations clinicians should be aware of?

One important point is convenience. Relacorilant is an oral medication, and patients only take it for a few days around each chemotherapy cycle. That makes it relatively easy to incorporate into treatment and less burdensome compared with continuous therapies. Combined with its tolerability, this convenience is meaningful for patients.

REFERENCES 

1. U.S. Food and Drug Administration. FDA approves relacorilant with nab-paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Published March 25, 2026. Accessed April 29, 2026. https://tinyurl.com/2zkp77vs

2. Lorusso D, Pignata S, Ferrandina G, et al. Overall survival with relacorilant and nab-paclitaxel in ovarian cancer. Lancet. 2026;[published online ahead of print]. doi:10.1016/S0140-6736(26)00462-9.

3. ClinicalTrials.gov. Relacorilant in combination with different treatment regimens in patients with gynecological cancers (BELLA). ClinicalTrials.gov identifier: NCT06906341. Updated October 22, 2025. Accessed April 29, 2026. https://tinyurl.com/5n7jpyn5