Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial
- PMID: 40473448
- DOI: 10.1016/S0140-6736(25)01040-2
Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): an open-label, randomised, controlled, phase 3 trial
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/m2 intravenously on days 1, 8, and 15 of each 28-day cycle) or nab-paclitaxel monotherapy (100 mg/m2 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.
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Conflict of interest statement
Declaration of interests AB reports consulting fees and support for attending meetings from MSD and AstraZeneca; payment or honoraria from MSD, AstraZeneca, and AbbVie; and participation on Data Safety Monitoring or Advisory Boards for MSD, GlaxoSmithKline (GSK), AstraZeneca, and AbbVie. AC reports support for the present manuscript from Corcept; grants or contracts from AstraZeneca, Advenchen, Eisai, Immunogen, MSD, and Mural Oncology; payment or honoraria from GSK; and participation on Data Safety Monitoring or Advisory Boards for GSK, and Immunogen. AD reports payment or honoraria from GSK and support for attending meetings from Gilead, Novartis, and AstraZeneca. AFdCC reports payment or honoraria from Roche, MSD, Daiichi, Adium, GSK, AstraZeneca, Pfizer, Amgen, and AbbVie; support for attending meetings from Roche, MSD, Daiichi, Adium, GSK, and AstraZeneca; and participation on Data Safety Monitoring or Advisory Boards for Roche, MSD, Daiichi, Adium, GSK, AstraZeneca, Pfizer, Amgen, and AbbVie. AK-H reports stock or stock options in Corcept and Exelixis. AMJ and SGP report support for the present manuscript, stock or stock options, and employment from Corcept. AO reports consulting fees from AbbVie, Agenus, AstraZeneca, Clovis, Corcept, Deciphera, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana, Myriad Genetics, Novocure, OncoXerna, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Stemline Therapeutics Sutro Biopharma, TORL Bio Therapeutics, Zentalis, and Zymeworks; payment or honoraria from the NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, the ESO, AstraZeneca, GSK; support for attending meetings from AstraZeneca, PharmaMar, and Roche; and participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Agenus, AstraZeneca, Clovis Oncology, Corcept, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana, Myriad Genetics, Novocure, OncoXerna, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Stemline Therapeutics Sutro Biopharma, TORL Bio Therapeutics, Zentalis, and Zymeworks. BJM reports consulting fees from AbbVie, Alkermes, AstraZeneca, BioNTech, Corcept, Daiichi Sankyo, Eisai, Genmab–Seagen–Pfizer, the Gynecologic Oncology Group Foundation, Gradalis, ImmunoGen–AbbVie, Incyte, Karyopharm, pharmaand, ProfoundBio, Regeneron, Roche–Genentech, Sutro Biopharma, Tubulis, Verastem Oncology, Zentalis, and Zymeworks; and payment or honoraria from AbbVie, AstraZeneca, BioNTech, Corcept, Daiichi Sankyo, Eisai, Genmab, Genmab–Seagen–Pfizer, the Gynecologic Oncology Group Foundation, GSK, ImmunoGen–AbbVie, Incyte, Karyopharm, Lilly, Mersana Therapeutics, MSD, Mural Oncology, Myriad Genetics, Natera, Novartis, Novocure, Onco4, Panavance, pharmaand, ProfoundBio, Regeneron, Roche–Genentech, Sutro Biopharma, Tubulis, Verastem, Zentalis, Zymeworks, AstraZeneca, Eisai, ImmunoGen–AbbVie, Lilly, MSD, and Tesaro–GSK. BS reports consulting fees from AbbVie, GSK, GenMab, Seagen, Pfizer, Novocure, Aadi, Gilead, Eisai, Merck, Incyte, and Regeneron. BY reports consulting fees from MSD, AstraZeneca, GSK–TESARO, Bayer, Roche–Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis, Merck Serono, Bristol Myers Squibb, Seagen, Myriad, Menarini, Gilead, Eisai, pharmaand, and AbbVie; and stock or stock options in See2Cure. CCa reports payment or honoraria from GSK and AstraZeneca. CD reports payment or honoraria from Pierre Fabre and The Limbic; support for attending meetings from GSK; and stock or stock options in Genesis Care. DL reports grants or contracts from AstraZeneca, Clovis, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Seagen, and Roche; consulting fees from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, Seagen, and Novartis; payment or honoraria from AstraZeneca, Clovis, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; support for attending meetings and/or travel from GSK, AstraZeneca, Clovis, and MSD; and participation on a Data Safety Monitoring or Advisory Board for AstraZeneca, Clovis, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro. DMO reports support for the present manuscript from Corcept; grants or contracts from AbbVie, Advaxis, Agenus, Alkermes, Aravive, Arcus, AstraZeneca, BeiGene, Boston Biomedical, Bristol Myers Squibb, Clovis, Deciphera Pharma, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GSK, the Gynecologic Oncology Group Foundation, F Hoffmann–La Roche, ImmunoGen, Incyte, IOVANCE, Karyopharm, Leap, the Ludwig Institute for Ca, Merck & Co, Merck Sharp & Dohme, Mersana, NCI, Novartis, NovoCure, NRG Oncology, OncoC4, OncoQuest, Pfizer, Precision Therapeutics, Prelude Therapeutics, Regeneron, the RTOG, Rubius Therapeutics, Seattle Genetics (SeaGen), Sutro Biopharma, SWOG, TESARO, and Verastem; consulting fees from AbbVie, AdaptImmune, Agenus, Arcus, AstraZeneca, Boston Biomedical, Cardiff Oncology, Celcuity, Corcept, Duality Bio, Eisai, Elevar, Exelixis, Genentech, Genelux, GSK, the Gynecologic Oncology Group Foundation, F Hoffmann–La Roche, ImmunoGen, Imvax, InterVenn, INXMED, IOVANCE, Janssen, Jazz Pharmaceuticals, Laekna, Merck & Co, Merck Sharp & Dohme, Mersana, Novartis, NovoCure, OncoC4, Onconova, Regeneron, RepImmune, R Pharm, Seattle Genetics (SeaGen), Sutro Biopharma, Verastem, VBL Therapeutics, Xencor, and Zentalis; participation on a Data Safety Monitoring Board or Advisory Board at Frantz Viral Therapeutics; and a leadership or fiduciary role at the Gynecologic Oncology Group Foundation Board of Directors. EH reports participation on a Data Safety Monitoring or Advisory Board for Immunogen. EM reports grants or contracts from Stanford Cancer Institute. GA reports payment or honoraria from GSK and AstraZeneca. HIP reports support for attending meetings, stock or stock options, and employment from Corcept. ICT reports a leadership or fiduciary role at BayArea Biotech Statistics Workshop and stock or stock options and employment from Corcept. IV reports consulting fees from Akesobio, Bristol Myers Squibb, Eisai, F Hoffmann–La Roche, Genmab, GSK, ITM Radiopharma, Karyopharm, MSD, Novocure, Oncoinvent, Sanofi, Regeneron, and Seagen; and participation on Data Safety Monitoring or Advisory Boards for AbbVie, Agenus, AstraZeneca, Corcept, Daiichi, F Hoffmann–La Roche, Immunogen, Kronos Bio, Mersana, Novartis, OncXerna, Verastem Oncology, and Zentalis. LB reports consulting fees and participation on Data Safety Monitoring or Advisory Boards for MDS, GSK, AstraZeneca, and AbbVie; payment or honoraria from MDS, GSK, AstraZeneca, AbbVie, pharmaand, and Merck; and support for attending meetings from MSD, AstraZeneca, and Merck. LGi reports grants or contracts from Alkermes, Ascendis, AstraZeneca, Bayer, CanariaBio, Corcept, Daiichi Kankyo, Eisai, Espersas, Fortrea, GmbH, the Gynecologic Oncology Group Foundation, GSK, ImmunoGen, IMV, K-Group Beta, Karyopharm, Merck, Mersana Therapeutics, Novocure, OncoQuest, Paraxel International, Pfizer, Pri-Wex Pharma, Repare Therapeutics, Roche, Seagen, Shattuck Labs, Sichuan Kelun Biotech Biopharma–Parexel, Sutro Bio Pharma, and Tesaro; consulting fees from Merck and GSK; payment or honoraria from GSK and Repare; support for attending meetings from Zentalis, GSK, Merck, the Gynecologic Oncology Group Foundation, and EndomEra; and participation in Advisory Board meetings for CabaruaBio, Corcept, Eisai, GSK, ImmnoGen, Karyopharm, Kora Health Care, Merck, and Novocure. MS reports consulting fees from MSD and AstraZeneca; payment or honoraria from MSD, GSK, AstraZeneca, and AbbVie; support for attending meetings from MSD, AstraZeneca, GSK, and Daiichi Sankyo; and participation on Data Safety Monitoring or Advisory Boards for MSD, GSK, AstraZeneca, and AbbVie. NC reports grants or contracts from AstraZeneca and Roche; payment or honoraria from AstraZeneca, GSK, MSD, and Eisai; participation on Data Safety Monitoring or Advisory Boards for AstraZeneca, Clovis, Eisai, GSK, ImmunoGen, Mersana, MSD–Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche, Novocure, Biontech, Gilead, and Genmab; and a leadership role as Chair of the Alleanza Contro il Tumore Ovarico (ACTO) Scientific Committee. SN reports consulting fees and participation on Data Safety Monitoring or Advisory Boards for AbbVie, GSK, AstraZeneca, and BioNtech; payment or honoraria from GSK and AstraZeneca; support for attending meetings from GSK, AstraZeneca, MSD, and AbbVie; a leadership or fiduciary role as Chair of the Gynae-oncology Group UK, ENGOT strategic committee; and stock or stock options in GSK and Haleon. TVG reports grants or contracts from Amgen, AstraZeneca, and Roche; consulting fees from AbbVie, AstraZeneca, BeiGene, BioNTech, Cancer Communications and Consultancy, Daiichi Sankyo, Eisai, Eli Lilly, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, MSD–Merck, OncXerna, Seagen, TORL Bio Therapeutics, Tubulis, Verastem, and Zentalis; honoraria for lectures from AbbVie, AstraZeneca, Eisai, GSK, ImmunoGen, and MSD; and support for attending meetings from ImmunoGen, MSD, and PharmaMar. VS reports consulting fees from Menarini, MDS, GSK, AstraZeneca, and AbbVie; payment or honoraria from MDS, GSK, AstraZeneca, AbbVie, pharmaand, and Eisai; support for attending meetings from Menarini, MSD, and AstraZeneca; and participation on Data Safety Monitoring or Advisory Boards for Menarini, MDS, GSK, AstraZeneca, AbbVie, and Eisai. All other authors declare no competing interests.
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