BELLA Trial Evaluates Potential Added Benefit of Bevacizumab Plus Relacorilant/Nab-Paclitaxel in Platinum-Resistant Ovarian Cancer

Providing effective and expansive treatment options remains a major therapeutic challenge in platinum-resistant ovarian cancer.¹ Despite initial responses to standard-of-care (SOC) platinum-based chemotherapy, approximately 80% of patients with advanced-stage ovarian cancer and up to 40% of those with endometrial cancer will relapse, and most patients with recurrent disease ultimately develop platinum resistance. This clinical scenario is particularly difficult given that historical treatment options in the platinum-resistant setting have largely been limited to sequential single-agent chemotherapy with or without bevacizumab (Avastin), and response rates with these regimens generally remain at approximately 15% or lower.²

Nab-paclitaxel (Abraxane) has demonstrated manageable safety and encouraging efficacy in patients with recurrent ovarian and endometrial cancers, supporting its use as a combination backbone in these settings.¹ Bevacizumab has also been shown to bolster responses with chemotherapy in ovarian cancer. However, even with its addition, response rates typically increase only to approximately 30%.²

Relacorilant is an oral, selective glucocorticoid receptor (GR) antagonist designed to enhance tumor sensitivity to cytotoxic chemotherapies such as nab-paclitaxel by inhibiting cortisol signaling through the GR.¹ Following the demonstration of its efficacy in combination with nab-paclitaxel in the phase 3 ROSELLA trial (NCT05257408), relacorilant is now being further evaluated with nab-paclitaxel and bevacizumab in the phase 2 BELLA study (NCT06906341).

“The BELLA study is an offshoot of ROSELLA,” Alexander B. Olawaiye, MD, a professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh Medical Center (UPMC) and director of gynecologic cancer research at Magee-Women’s Hospital of UPMC in Pennsylvania, explained in an interview with OncLive. “We know from [data from] previous studies that bevacizumab in addition to chemotherapy does improve the efficacy of the chemotherapy. If the addition of bevacizumab to relacorilant and nab-paclitaxel could improve the regimen’s efficacy, we do not want patients to miss out on that. Therefore, even though it’s a phase 2 trial, BELLA is very important.”

What early-phase evidence provided proof of concept for relacorilant in platinum-resistant ovarian cancer?

Activation of the GR pathway through cortisol binding has been implicated in the development of chemoresistance.^1,2 High GR expression, which is common in ovarian tumors, has also been associated with poorer patient prognosis. Preclinical and early-phase clinical data suggest that GR antagonism with relacorilant can counteract cortisol’s antiapoptotic effects.²

“It’s a first-in-class drug,” Olawaiye stated. “Steroids are very popular in cancer treatment, whether as part of the therapeutic regimen or as part of the supportive regimen in patients having reactions or having nausea, or maybe to prevent or reduce the risk of those things. It is very interesting that this drug, which essentially blocks the pathway by which steroids work, can be an effective treatment for [patients with] cancer.”

Data from a phase 1 dose-escalation study (NCT02762981) showed that in heavily pretreated patients with advanced or metastatic solid tumors, 33% of response-evaluable patients (n = 57) achieved durable disease control lasting at least 16 weeks with relacorilant plus nab-paclitaxel.³ Additionally, 28.6% of patients (n = 42) experienced a longer duration of benefit compared with a prior taxane.

Subsequently, findings from a phase 1/2 trial (NCT03776812) demonstrated that intermittent dosing of relacorilant plus nab-paclitaxel (n = 60) prolonged progression-free survival (PFS) and duration of response (DOR) compared with nab-paclitaxel alone (n = 60) in patients with platinum-resistant or platinum-refractory ovarian cancer who had received no more than 4 prior lines of chemotherapy.⁴ A trend toward improved overall survival (OS) was also observed. These findings provided the rationale for the confirmatory phase 3 ROSELLA trial.

How did ROSELLA data validate the efficacy and safety of this combination?

ROSELLA was a randomized, 2-arm, open-label, multicenter, global study enrolling patients at least 18 years of age with confirmed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers who had prior exposure to between 1 and 3 systemic anticancer therapies or at least 1 prior line of platinum-based chemotherapy and bevacizumab.⁵ The study was initiated in June 2022 and completed recruitment as of April 8, 2024.⁶ A total of 381 patients were enrolled at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada, and Australia.

Findings presented during the 2025 American Society of Clinical Oncology Annual Meeting and simultaneously published in The Lancet showed that relacorilant plus nab-paclitaxel reduced the risk of disease progression or death by 30% vs nab-paclitaxel alone (HR, 0.70; 95% CI, 0.54-0.91; P = .0076).⁷ The median PFS with these respective regimens was 6.54 months (95% CI, 5.55-7.43) compared with 5.52 months (95% CI, 3.94-5.88). The 6-month PFS rates were 52% and 42%, respectively, and the 12-month PFS rates were 25% and 13%, respectively.

Moreover, at the interim OS analysis (50% data maturity), the combination also demonstrated a clinically meaningful improvement vs nab-paclitaxel. The median OS was 15.97 months (95% CI, 13.47-not reached) with relacorilant plus nab-paclitaxel vs 11.50 months (95% CI, 10.02-13.57) for nab-paclitaxel alone (HR, 0.69; 95% CI, 0.52-0.92; nominal P = .0121). The 12-month OS rates were 60% and 49%, respectively.

“The PFS [benefit with relacorilant plus nab-paclitaxel] was highly statistically significant, demonstrating that the combination showed a meaningful reduction in the risk of progression and death,” Olawaiye reported. He added, “Even though the OS data were not mature, they also showed a meaningful reduction in the risk of death.”

At the 2025 European Society for Medical Oncology (ESMO) Congress, updated results from a prespecified subgroup analysis of ROSELLA showed consistent benefit among patients previously treated with PARP inhibitors.⁸ In this subgroup, relacorilant plus nab-paclitaxel achieved a median blinded independent central review–assessed PFS of 7.36 months (95% CI, 5.59-8.18) vs 4.63 months (95% CI, 3.55-5.72) with nab-paclitaxel alone (n = 120; HR, 0.60; 95% CI, 0.42-0.85; nominal P = .0035). Among patients who had progressed on a prior PARP inhibitor, the median PFS was 7.36 months (95% CI, 5.39-8.44) vs 3.94 months (95% CI, 3.32-5.72) with nab-paclitaxel alone (n = 97; HR, 0.56; 95% CI, 0.37-0.84; nominal P = .0046).

“A large number of patients [who] were treated in the ROSELLA study had not only been treated with PARP inhibitors, but had progressed on PARP inhibitors,” Olawaiye noted. “We basically chose a difficult population of patients to study, and the combination still demonstrated a high response rate and statistically significant PFS [benefit]. We’re hopeful that we will achieve an OS [benefit in this subgroup] as well.”

Regarding safety, ascites occurred less frequently with the combination (any-grade, 5%; grade ≥ 3, 3%) vs monotherapy (11%; 5%).⁷ Treatment-emergent adverse effects (AEs) occurred in nearly all patients, with grade 3 or higher AEs reported in 74.5% of patients treated with the combination (n = 188) and 59.5% with monotherapy (n = 190). Serious AEs occurred in 35.1% and 23.7% of patients, respectively. No fatal AEs were attributed to relacorilant.

“In the overall population, we did not see any new safety signals that could be ascribed to relacorilant; most of the toxicities that we saw on ROSELLA were well-known toxicities of nab-paclitaxel,” Olawaiye noted. “For those who received relacorilant, those toxicities were slightly worse, but that was because of the extended period of time for which they remained on nab-paclitaxel because they were doing better than the control arm. When we adjusted for the length of time on nab-paclitaxel, the difference in toxicity between the 2 arms disappeared.”

How is the BELLA trial designed?

BELLA is an open-label, global, multi-arm study evaluating the potential added benefit of combining relacorilant plus nab-paclitaxel with bevacizumab in ovarian cancer and relacorilant plus nab-paclitaxel in endometrial cancer.¹ Following the readout of subgroup data at the 2025 ESMO Congress, Corcept Therapeutics, the drug’s developer, announced it was expanding the BELLA trial to include 3 study arms for patients with platinum-resistant ovarian cancer (arm A), platinum-sensitive ovarian cancer (arm B), and endometrial cancer (arm C).⁹

Across all 3 arms, patients must be 18 years or older and have an ECOG performance status of 0 to 1, a life expectancy of at least 3 months, and a least 1 measurable target lesion per RECIST 1.1 criteria.¹ Eligibility criteria for arms A/B include high-grade serous/endometrioid, epithelial ovarian, primary peritoneal, or fallopian-tube carcinoma; prior exposure to between 1 and 3 lines of anticancer therapy; and 1 or more prior lines of platinum-containing therapy. In arm A, platinum-resistant disease is defined as progression no more than 183 days from the last dose of platinum therapy. In arm B, platinum-sensitive disease is defined as progression at least 183 days from the last dose of platinum chemotherapy and radiographic progression while on a prior PARP inhibitor. Prior treatment with bevacizumab is permitted in both arms. Patients with a BRCA1/2 mutation must have received a PARP inhibitor, unless it was unsuitable for them or they were unable to access it.

In arm C, patients must have stage III or IV recurrent or metastatic histologically or cytologically confirmed endometrial cancer with endometrioid, clear cell, or serous histology, or mixed histology including these subtypes. Patients must also have had prior exposure to 1 or 2 lines of anticancer treatment, at least 1 line of platinum-containing therapy, and approved anti–PD-1/PD-L1 inhibitors.

“In ROSELLA, patients must have been [previously] exposed to bevacizumab…but the trial [regimen] did not include bevacizumab,” Olawaiye noted. “In BELLA, ...patients who are both bevacizumab-naive or -exposed [are permitted to enroll]. This will allow us to see if the addition of bevacizumab to relacorilant and nab-paclitaxel, which we have [already] demonstrated is a good combination, would [boost efficacy] in patients with ovarian cancer.”

Investigators plan to enroll approximately 90 patients into each treatment arm. In arms A and B, patients will receive oral relacorilant at 150 mg on days 1, 2, 7 through 9, 14 through 16, 21, and 28; intravenous (IV) nab-paclitaxel at 80 mg/m² on days 1, 8, and 15; and IV bevacizumab at 10 mg/kg on days 1 and 15 of a 28-day cycle. Patients in arm C will only receive relacorilant plus nab-paclitaxel in the same dosing schedule.

The study’s primary end point is investigator-assessed PFS per RECIST 1.1 criteria. Key secondary end points include overall response rate, best overall response, DOR, clinical benefit rate at 24 weeks, OS, and safety.

BELLA is being conducted at approximately 50 locations in the US, Europe, and South Korea.

“We’re excited about BELLA,” Olawaiye reiterated. "In most cases, when a patient [with ovarian cancer] is coming up to their second or third line of therapy, they would have been treated with bevacizumab. We want to make sure that we get the maximum efficacy out of this regimen.”

What regulatory developments are next for relacorilant?

In September 2025, the FDA accepted a new drug application seeking approval of relacorilant for use in patients with platinum-resistant ovarian cancer based on findings from ROSELLA.¹⁰ The regulatory agency has set a Prescription Drug User Fee Act decision date of July 11, 2026.

Of note, a marketing authorization application for the use of relacorilant in platinum-resistant ovarian cancer was also submitted to the European Medicines Agency in October 2025.¹¹

“I’m hopeful that my colleagues are as excited about this new regimen as I am,” Olawaiye concluded. “It’s actually a non–biomarker selected regimen, so if it gets approved, there is no test that we need to administer to [ensure] patients can qualify for it, and it will be applicable to basically all groups of patients that have platinum-resistant ovarian cancer. That would make it a very useful addition [to the treatment paradigm].”

References

1. Lorusso D, Monk BJ, Park JY, et al. BELLA: a phase II study of relacorilant plus nab-paclitaxel and bevacizumab in patients with platinum-resistant ovarian cancer. Ann Oncol. 2025;36(suppl 2):S748. doi:10.1016/j.annonc.2025.09.057
2. Olawaiye AB, Kim JW, Bagameri A, et al. Clinical trial protocol for ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in advanced platinum-resistant ovarian cancer. J Gynecol Oncol. 2024;35(4):e111. doi:10.3802/jgo.2024.35.e111
3. Munster PN, Greenstein AE, Fleming GF, et al. Overcoming taxane resistance: preclinical and phase 1 studies of relacorilant, a selective glucocorticoid receptor nodulator, with nab-paclitaxel in solid tumors. Clin Cancer Res. 2022;28(15):3214-3224. doi:10.1158/1078-0432.CCR-21-4363
4. Colombo N, Van Gorp T, Matulonis UA, et al. Relacorilant + nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer: a three-arm, randomized, controlled, open-label phase II study. J Clin Oncol. 2023;41(30):4779-4789. doi:10.1200/JCO.22.02624
5. Relacorilant in combination with nab-paclitaxel in advanced, platinum-resistant, high-grade epithelial ovarian, primary peritoneal, or fallopian-tube cancer. ClinicalTrials.gov. Updated April 16, 2025. Accessed December 16, 2025. https://clinicaltrials.gov/study/NCT05257408
6. Corcept completes enrollment in pivotal phase 3 ROSELLA trial of relacorilant in patients with platinum-resistant ovarian cancer. News release. Corcept Therapeutics Incorporated. April 8, 2024. Accessed December 16, 2025. https://ir.corcept.com/news-releases/news-release-details/corcept-completes-enrollment-pivotal-phase-3-rosella-trial
7. Olawaiye AB, Gladieff L, Gilbert L, et al. ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG-3073, ENGOT-ov72). J Clin Oncol. 2025;43(suppl 17):LBA5507. doi:10.1200/JCO.2025.43.17_suppl.LBA5507
8. Lorusso D, Quesada S, Chan JK, et al. ROSELLA (GOG3073, ENGOTov72, APGOT-OV10): relacorilant + nab-paclitaxel in the subgroup of patients with platinum-resistant ovarian cancer (PROC) previously exposed to a PARP inhibitor. Ann Oncol. 2025;36(suppl 2):S1703-S1704. doi:10.1016/j.annonc.2025.09.057
9. Corcept presents ESMO 2025 late-breaker: relacorilant demonstrates benefit in patients with platinum-resistant ovarian cancer with prior PARP inhibitor treatment. News release. Corcept Therapeutics Incorporated. October 19, 2025. Accessed December 16, 2025. https://ir.corcept.com/news-releases/news-release-details/corcept-presents-esmo-2025-late-breaker-relacorilant
10. FDA files Corcept’s new drug application for relacorilant as a treatment for patients with platinum-resistant ovarian cancer. News release. Corcept Therapeutics Incorporated. September 10, 2025. Accessed December 16, 2025. https://ir.corcept.com/news-releases/news-release-details/fda-files-corcepts-new-drug-application-relacorilant-treatment-0
11. Corcept submits marketing authorization application to European Medicines Agency for relacorilant as a treatment for patients with platinum-resistant ovarian cancer. News release. Corcept Therapeutics Incorporated. October 14, 2025. Accessed December 16, 2025. https://ir.corcept.com/news-releases/news-release-details/corcept-submits-marketing-authorization-application-european