Abstract 536P
Background
Therapy options for patients with recurrent, platinum-resistant ovarian cancer are limited. Cortisol contributes to chemotherapy resistance, one driver of poor outcomes, by suppressing apoptotic pathways used by cytotoxic agents. A phase 2 study of relacorilant (RELA) + nab-paclitaxel (NP) in patients with ovarian cancer has shown that glucocorticoid receptor modulation with RELA can improve the efficacy of NP. In all patients, intermittent RELA + NP significantly improved progression-free survival (PFS) and improved overall survival (OS) without additional side-effect burden. We present results in the subgroup mirroring the patient population of an upcoming phase 3 study.
Methods
178 women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma with ≤4 prior lines of chemotherapy were enrolled in a phase 2, open-label, randomized study of 2 RELA dosing schedules + NP vs NP alone (NCT03776812). The subgroup of patients without primary platinum-refractory disease and with 1-3 prior lines of therapy (“phase 3 population”) comprised 137 patients, of whom 46 received NP (80 mg/m2) + intermittent RELA (150 mg QD the day before, of, and after NP) and 50 received NP alone (100 mg/m2). NP was administered on days 1, 8, and 15 of each 28-day cycle.
Results
In this subgroup, intermittent RELA + NP resulted in improvements vs NP alone in PFS (HR 0.58, 95% CI 0.37-0.91, log-rank P=0.0162; median PFS 5.6 vs 3.8 mo); duration of response (DoR; HR 0.26, 95% CI 0.11-0.62, log-rank P=0.0009; median DoR 5.6 vs 3.6 mo); and OS (HR 0.52, 95% CI 0.31-0.86, log-rank P=0.0097; median OS 13.9 vs 12.2 mo). Objective response rates were similar and numerically favored RELA + NP (41.9% vs 38.6%).
Conclusions
In addition to the improvements seen in all patients, intermittent RELA + NP improved PFS, OS, and DoR in the “phase 3 population” subgroup. This confirms the potential of intermittent RELA + NP in this patient population, which will be studied further in an upcoming phase 3 trial (ROSELLA, NCT05257408).
Clinical trial identification
NCT03776812.
Editorial acknowledgement
Writing and editorial support for this abstract was provided by Tina Schlafly, PhD, an employee of Corcept Therapeutics.
Legal entity responsible for the study
Corcept Therapeutics.
Funding
Corcept Therapeutics.
Disclosure
N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, Biocad, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO(Alleanza contro il tumore ovarico). T. Van Gorp: Financial Interests, Institutional, Advisory Board, Apr-2021: MSD; Financial Interests, Institutional, Advisory Board, May-2021 until Dec-2021: GSK; Financial Interests, Institutional, Advisory Board, Feb-2021: OncXerna Therapeutics; Financial Interests, Institutional, Advisory Board, Jan-2021: Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant, Oct-2020 until Oct-2021: Amgen; Financial Interests, Institutional, Research Grant, Oct-2020 onwards: Roche. U.A. Matulonis: Financial Interests, Personal, Research Grant: Corcept Therapeutics. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, ImmunoGen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. R.N. Grisham: Financial Interests, Personal, Other, Consulting fee: GSK, AZ, Signatera, Verastem, SpringWorks, Corcept. G. Fleming: Financial Interests, Personal, Research Grant: GSK, Roche, Syros, Iovance, AZ, Compugen, K group beta, Astellas, CytomX; Financial Interests, Personal, Advisory Board: GSK. A. Olawaiye: Financial Interests, Personal, Research Grant: Corcept Therapeutics. I.C. Tudor: Financial Interests, Personal, Full or part-time Employment: Corcept Therapeutics; Financial Interests, Personal, Stocks/Shares: Corcept Therapeutics. H.I. Pashova: Financial Interests, Personal, Full or part-time Employment: Corcept Therapeutics; Financial Interests, Personal, Stocks/Shares: Corcept Therapeutics. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG.