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Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial

Olawaiye, A. B.
; 
Gladieff, L.
; 
O'Malley, D. M.
; 
Kim, J. W.
; 
Garbaos, G.
; 
Salutari, V.
; 
Gilbert, L.
; 
Mileshkin, L.
; 
Devaux, A.
; 
Hopp, E.
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Abstract
BACKGROUND: Relacorilant, a first-in-class selective glucocorticoid receptor antagonist, increases a tumour's sensitivity to chemotherapy by reducing cortisol signalling. This study aimed to show whether the addition of relacorilant to nab-paclitaxel improves progression-free and overall survival in females with platinum-resistant ovarian cancer. METHODS: This randomised, controlled, open-label phase 3 trial (ROSELLA [GOG-3073/ENGOT-ov72]) was done at 117 hospitals and community oncology treatment centres in 14 countries across Australia, Europe, Latin America, North America, and South Korea. Patients had to be aged 18 years or older and had to have a confirmed diagnosis of platinum-resistant, epithelial (ie, high-grade serous, endometrioid, or carcinosarcoma with a ≥30% epithelial component) ovarian, primary peritoneal, or fallopian tube cancer; up to three previous lines of anticancer therapy and previous bevacizumab and disease progression or intolerance to the most recent therapy; measurable disease according to the Response Evaluation Criteria in Solid Tumours (RECIST; version 1.1); an Eastern Cooperative Oncology Group performance status of 0 or 1; and adequate organ function. Patients were assigned (1:1) to relacorilant (150 mg orally the day before, of, and after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m(2) intravenously on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel monotherapy (100 mg/m(2) intravenously on the aforementioned schedule). The dual primary endpoints were progression-free survival assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours (version 1.1) and overall survival, and were assessed in all randomly assigned patients by intention to treat. The safety population included all randomly assigned patients who received at least one dose of the assigned treatment. This trial was registered at ClinicalTrials.gov, NCT05257408, and is ongoing. FINDINGS: Between Jan 5, 2023, and April 8, 2024, 381 patients were randomly assigned to the combination group (n=188) or to the nab-paclitaxel monotherapy group (n=193). Patients receiving relacorilant plus nab-paclitaxel had a statistically significant improvement in progression-free survival assessed by blinded independent central review compared with those receiving nab-paclitaxel monotherapy (hazard ratio 0·70 [95% CI 0·54-0·91]; median 6·54 months [95% CI 5·55-7·43] vs 5·52 months [3·94-5·88]; stratified log-rank p=0·0076). At the planned interim analysis, there was a clinically meaningful difference in overall survival with the addition of relacorilant to nab-paclitaxel (0·69 [95% CI 0·52-0·92]; 15·97 months [95% CI 13·47-not reached] vs 11·50 months [10·02-13·57]; log-rank p=0·0121). Adverse events were similar across study groups when adjusted for nab-paclitaxel exposure; no new safety signals were observed. INTERPRETATION: The addition of relacorilant to nab-paclitaxel prolonged progression-free survival and interim results also showed an improvement in overall survival. Together, the results position the combination of relacorilant and nab-paclitaxel as a potential new standard treatment for patients with platinum-resistant ovarian cancer. FUNDING: Corcept Therapeutics.
Authors
Olawaiye, A. B.
Gladieff, L.
O'Malley, D. M.
Kim, J. W.
Garbaos, G.
Salutari, V.
Gilbert, L.
Mileshkin, L.
Devaux, A.
Hopp, E.
Lee, Y. J.
Oaknin, A.
Scaranti, M.
Kim, B. G.
Colombo, N.
McCollum, M. E.
Diakos, C.
Clamp, A.
Leiser, A. L.
Balázs, B.
Monk, B. J.
Scandurra, G.
McClung, E.
Kaczmarek, E.
Slomovitz, B.
De La Cueva, H.
de Carvalho Calabrich, A. F.
Cassani, C.
You, B.
Van Gorp, T.
Churruca, C.
Caruso, G.
Nicum, S.
Bagaméri, A.
Artioli, G.
Bodnar, L.
Kang, S.
Vergote, I.
Kesner-Hays, A.
Pashova, H. I.
Pai, S. G.
Tudor, I. C.
Jubb, A. M.
Lorusso, D.
Affiliation
University of Pittsburgh School of Medicine and UPMC Magee-Women's Hospital, Gynecologic Oncology Group, Pittsburgh, PA, USA. Electronic address: olawaiyea@upmc.edu. Oncopole Claudius Regaud IUCT-Oncopole, Toulouse, France; GINECO, Paris, France. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea. Instituto Médico de la Fundación Estudios Clínicos, Santa Fe, Argentina. Department of Woman, Child, and Public Health, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy. Division of Gynecologic Oncology, Research Institute, McGill University Health Centre, Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Oncology Department of Grand Hôpital de Charleroi, Charleroi, Belgium; Belgium and Luxembourg Gynaecological Oncology Group, Leuven, Belgium. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA. Yonsei University College of Medicine, Seoul, South Korea. Medical Oncology Service, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain. DASA Oncologia, Hospital 9 de Julho, São Paulo, Brazil. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Gynecologic Oncology Program, European Institute of Oncology, IRCCS, Milan, Italy; Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy. Virginia Oncology Associates, Norfolk, VA, USA. Royal North Shore Hospital, St Leonards, NSW, Australia. The Christie NHS Foundation Trust, Manchester, UK; University of Manchester, Manchester, UK. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Department of Gynecology, Hungarian National Institute of Oncology, Budapest, Hungary. Florida Cancer Specialists and Research Institute, West Palm Beach, FL, USA. Medical Oncology Unit, Cannizzaro Hospital, Catania, Italy; Faculty of Medicine, Kore University of Enna, Enna, Italy. Stanford University, Palo Alto, CA, USA. Centre Oscar Lambret, Lille, France; GINECO, Paris, France. Mount Sinai Comprehensive Cancer Center, Miami Beach, FL, USA. Hospital La Fe Valencia, Valencia, Spain. Ensino e Terapia de Inovação Clínica AMO-ETICA, Salvador, Brazil. Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy; Unit of Obstetrics and Gynecology, IRCCS San Matteo Foundation, Pavia, Italy. GINECO, Paris, France; Lyon University Hospital (HCL), Lyon, France. University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium; Belgium and Luxembourg Gynaecological Oncology Group, Leuven, Belgium. Hospital Donostia, San Sebastián, Spain. Gynecologic Oncology Program, European Institute of Oncology, IRCCS, Milan, Italy; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. University College Hospital, London, UK. Azienda ULSS2 Marca Trevigiana, Treviso, Italy. Institute of Health Sciences, University of Siedlce, Siedlce, Poland. Department of Cancer Control and Population Health, National Cancer Center, Goyang, South Korea. Department of Gynecologic Oncology, University Hospital Leuven, Leuven, Belgium. Corcept Therapeutics, Redwood City, CA, USA. Department of Biomedical Science, Humanitas University, Pieve Emanuele, Italy; Humanitas San Pio X Hospital, Milan, Italy.
Description
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2025
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All Christie Publications
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Article
Citation
Olawaiye AB, Gladieff L, O'Malley DM, Kim JW, Garbaos G, Salutari V, et al. Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial. Lancet. 2025 Jun 21;405(10496):2205-16. PubMed PMID: 40473448. Epub 2025/06/06. eng.
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https://christie.openrepository.com/handle/10541/628064
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