A groundbreaking development in ovarian cancer treatment has emerged from the ROSELLA phase 3 trial, where the repurposed drug relacorilant, a selective glucocorticoid receptor antagonist (GR antagonist), combined with nab-paclitaxel, demonstrated significant survival benefits for patients with platinum-resistant ovarian cancer (PROC). This aggressive form of the disease, which affects women after their tumours no longer respond to standard platinum-based chemotherapy, saw a 35% reduction in the risk of death and a median overall survival extension of 4.1 months—from 11.9 months to 16 months.
The trial's success, published in The Lancet and highlighted in recent UK media, underscores the potential of drug repurposing to address unmet needs in oncology. Originally approved for Cushing's syndrome, relacorilant works by blocking the glucocorticoid receptor, a pathway cancer cells exploit under chemotherapy stress to evade cell death. This mechanism restores tumour sensitivity to nab-paclitaxel, a taxane chemotherapy agent, without requiring biomarker testing.
ROSELLA Trial: Design and Key Results
The ROSELLA trial (NCT05257408), an international multicentre study involving 381 women with recurrent PROC who had received 1-3 prior lines of therapy including bevacizumab, randomised patients 1:1 to relacorilant plus nab-paclitaxel or nab-paclitaxel alone. Dosing for relacorilant was intermittent—150 mg orally the day before, day of, and day after nab-paclitaxel (80 mg/m² IV on days 1, 8, 15 of 28-day cycles)—to minimise side effects.
Dual primary endpoints were met: progression-free survival (PFS) hazard ratio (HR) 0.70 (median 6.5 vs 5.5 months, p=0.0076) and overall survival (OS) HR 0.65 (p=0.0004). Benefits were consistent across subgroups, including those with prior PARP inhibitors (61% of patients). Safety profiles were comparable, with higher grade 3+ neutropenia (44% vs 25%) managed via dose adjustments and growth factors.
Following PFS success at ASCO 2025, OS data confirmed in January 2026 led to FDA approval in March 2026 as Lifyorli (relacorilant) plus nab-paclitaxel—the first GR antagonist for ovarian cancer.
UK Involvement in the ROSELLA Trial and Beyond
UK sites played a vital role in ROSELLA, including The Christie NHS Foundation Trust and University of Manchester, and University College London Hospitals (UCLH, affiliated with University College London). Contributors like BJM from Manchester highlight UK expertise in gynaecological oncology trials.
Manchester's Division of Cancer Sciences and UCL Cancer Institute exemplify UK higher education's contributions to global trials. The Christie, ranked among Europe's top cancer centres, integrates trial data into clinical practice, advancing precision medicine.
Target Ovarian Cancer lists ROSELLA as active in the UK, emphasising its relevance for the 7,600 annual UK diagnoses.Learn more about UK trial sites
The Ovarian Cancer Burden in the United Kingdom
Ovarian cancer remains the sixth most common cancer in UK women, with around 7,600 new cases and 4,000 deaths yearly—that's 11 women daily. Incidence is projected to rise 5% by 2038-2040, while mortality falls 14% due to advances like PARP inhibitors. However, PROC affects 20-30% of patients, with median survival under 12 months.
1-year net survival is 68%, 5-year 31%, lagging due to late diagnosis (70% stage 3/4). Repurposed therapies like relacorilant could bridge gaps, especially post-bevacizumab failure.
UK Universities Pioneering Repurposed Drug Research
UK higher education leads in repurposed drugs for ovarian cancer. Queen's University Belfast screens approved compounds for PROC synergies. Cardiff University explores paused cell targeting to overcome chemotherapy resistance, published in Nature Aging 2026.
The Institute of Cancer Research (ICR, London) develops idetrexed, a folate pathway inhibitor for high-grade serous ovarian cancer. University of Cambridge's £1M AI project personalises care using global data. Edinburgh's serous ovarian cancer initiative funds trametinib response studies.
Manchester and Imperial College London advance GR modulation and immune therapies, aligning with relacorilant's mechanism.
Mechanism of Action: Countering Chemotherapy Resistance
Cancer cells activate glucocorticoid receptors under stress, promoting survival via anti-apoptotic genes. Relacorilant selectively antagonises GR, sensitising cells to nab-paclitaxel-induced death without systemic cortisol disruption. Phase 2 ROGUESS confirmed PFS benefits; ROSELLA validated OS.
- Intermittent dosing minimises hyperglycaemia/adrenal risks.
- No biomarker needed, unlike PARP inhibitors (BRCA status).
- Synergy with taxanes addresses PROC heterogeneity.
Safety Profile and Manageability
Combination safety mirrored nab-paclitaxel, with exposure-adjusted rates overlapping. Neutropenia managed prophylactically; no new signals like adrenal crisis. Quality of life stable per EORTC questionnaires.
UK oncologists note feasibility for NHS integration post-EMA review.
Implications for UK Higher Education and Research Careers
This trial spotlights UK universities' global impact. Manchester's BJM co-authored Lancet paper, fostering PhD/postdoc opportunities in pharmacogenomics.Explore ovarian cancer research jobs at UK universities
ICR and Cambridge seek talent in AI-drug discovery. Repurposing accelerates translation, suiting early-career researchers. Funding from CRUK/NIHR supports trials, enhancing employability.
Future Outlook: EMA Approval and UK Trials
Post-FDA approval, EMA filing expected; UK sites prepare for rollout. BELLA trial explores relacorilant + pembrolizumab. UK-led studies on GR in combination therapies continue.
With rising incidence, repurposing via UK academia could transform outcomes, reducing NHS burden (£200M+ annually).
Photo by Marija Zaric on Unsplash
Stakeholder Perspectives and Patient Impact
Target Ovarian Cancer welcomes data; patients gain hope for 4+ months. Oncologists like Manchester's praise biomarker-free access. Students: hands-on trials build skills.