Introduction/Background Single agent chemotherapies are commonly used in platinum-resistant ovarian cancer, but outcomes are generally poor. Cortisol, which acts by binding to the glucocorticoid receptor (GR), can suppress apoptotic pathways used by cytotoxic agents. The GR is abundantly expressed in ovarian tumours and high GR expression is associated with poor outcomes. Data indicate that the selective GR modulator relacorilant can reverse cortisol’s anti-apoptotic effects, thereby enhancing chemotherapy efficacy. In a phase 2 study in patients with recurrent, platinum-refractory or platinum-resistant ovarian cancer, intermittently dosed relacorilant + nab-paclitaxel showed clinically meaningful improvement in progression-free survival (PFS), duration of response (DoR), and a trend toward improved overall survival (OS) without increased side effect burden compared to nab-paclitaxel monotherapy. This phase 3 study aims to confirm the findings of the phase 2 study in a larger patient population.
Methodology ROSELLA (GOG-3073, ENGOT-Ov72/MITO, NCT05257408) is a randomised, phase 3, 2-arm, open-label study of relacorilant + nab-paclitaxel vs nab-paclitaxel monotherapy. Women with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer who have received 1–3 lines of prior systemic anticancer therapy, including prior bevacizumab, and at least 1 line of platinum-based therapy are being enrolled. Patients with primary platinum-refractory disease are excluded from the trial. Approximately 360 patients are being randomised 1:1 to relacorilant (150 mg the day before, of, and after nab paclitaxel infusion) + nab-paclitaxel (80 mg/m<sup>2</sup>) or nab paclitaxel monotherapy (100 mg/m<sup>2</sup>). Nab-paclitaxel is administered on days 1, 8, and 15 of each 28-day cycle. Stratification factors are prior lines of therapy (1 vs >1) and region of world (North America vs. Europe vs. rest of world).
Results The primary endpoint is PFS assessed by blinded independent central review. Key secondary endpoints include OS, PFS by investigator assessment, objective response rate, best overall response, DoR, safety, pharmacokinetics, pharmacodynamics, patient-reported outcomes, and quality of life.
Disclosures DL reports receipt of grants/research supports from Clovis Oncology, GSK, MSD, PharmaMa, AstraZeneca, genmab, Immunogen, Incyte, Roche, Seagen, and Novartis; receipt of honoraria or consultation fees from Clovis Oncology, GSK, MSD, PharmaMa, AstraZeneca, genmab, Immunogen, Seagen, Novartis, Oncoinvest, Corcept, and Sutro; participation in a company sponsored speaker’s bureau for Seagen, Immunogen, Genmab,AstraZzeneca, Clovis Oncology, GSK, MSD and PharmaMar; and travel expenses from AstraZeneca, Clovis Oncology, GSK. AB reports receipt of honoraria or consultation fees from Astra-Zeneca. LG reports receipt of honoraria or consultation fees from, and participation in a company sponsored speaker’s bureau for Astra-Zeneca, GSK, MSD, and Esai. LM reports receipt of funding for investigator-initiated trial from BeiGene. BJM reports honoraria for serving as a consultant to Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieres, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, and Zentalis; and reports honoraria for speaker/consultant roles for AstraZeneca, Clovis, Esai, Merck, Roche/Genentech, and Tesaro/GSK. SN reports receipt of grants/research from AstraZeneca and GSK; receipt of honoraria or consultation fees from AstraZeneca, GSK, Clovis, and MSD; participation in a company sponsored speaker’s bureau for AstraZeneca and GSK; and spouse/partner shared with AstraZeneca and GSK. AN-R reports receipt of honoraria or consultation fees from AZ, Roche, Daiichi, Eisai, MSD, Pfizer and Libbs; and participation in a company sponsored speaker’s bureau for AZ, Roche, Daiichi, Eisai, MSD, Pfizer, Libbs, and Gilead. AO reports receipt of honoraria or consultation fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, and F. Hoffmann-La Roche; and travel and accommodation from Astra Zeneca, PharmMar, and Roche. DO’M reports institution received funds for research from Abbvie, Advaxis, Agenus Inc, Alkermes, Aravive, Inc, Arcus Biosciences, AstraZeneca, BeiGene USA Inc., Boston Biomedical, Bristol Meyers Scribb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serano, Inc., Exelixis, Genentech, Inc., Genmab, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche Inc.,ImmunoGen, Inc., Incyte Corporation, IOVANCE Biotherapeutics, Karyopharm, Leap Therapeutics, Inc., Ludwig Institute for Ca, Merck & Co, Merck Sharpe & Dohme Corp, Mersana Therapeutics, Inc, NCI, Novartis, NovoCure, NRG Oncology, OncoC4, Inc., OncoQuest Inc., Pfizer Inc., Precision Therapeutics, Inc., Prelude Therapeutics, Regeneron Pharmaceuticals, Inc., RTOG, Rubius Therapeutics, Seattle Genetics (SeaGen), Sutro Biopharma, SWOG, TESARO, and Verastem, Inc.; and reports receipt of personal fees for consultation and/or advisory boards from Abbvie, AdaptImmune, Agenus, Inc., Arquer Biosciences, Inc., AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar, Exelixix, Genentech Inc., Genulux, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche Inc., ImmunoGen, Inc., Imvax, InterVenn, INXMED, IOVANCE Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Luzsana Biotechnology, Merck & Co, Merck Sharpe & Dohme Corp., Mesana Therapeutics, Inc., Myriad, Novartis, NovoCure, OncoC4, Inc., Onconova, Regeneron Pharmaceuticals, Inc., RepImmune, R Pharm, Roche Diagnostics, Seattle Genetics (SeaGen), Sorrento, Sutro Biopharma, Tarveda Therapeutics, Toray, Trillium, Umoja, Verstem, Inc., VBL Therapeutics, Vincerx Pharma, Xencor, and Zentalis. LD reports Corcept stock/stock options. ABO reports receipt of grants/research support from Corcept and AstraZeneca; and receipt of honoraria or consultation fees from AZ, GSK, Merck, and Genentech. EB, AC-G, AD, MEG, J-WK, JK, MEMcC, MO, ICT and X have no potential conflicts of interest to report.
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