721O - Relacorilant, a selective glucocorticoid receptor modulator, in combination with nab-paclitaxel improves progression-free survival in patients with recurrent platinum-resistant ovarian cancer: A 3-arm, randomized, open-label, phase II study

Background

Pre-clinical and clinical data indicate that glucocorticoid receptor (GR) antagonism may enhance/restore chemotherapy sensitivity. This is the first randomized, controlled study to explore the efficacy and safety of relacorilant (RELA), a selective GR modulator, in combination w/ nab-paclitaxel (nab-pac) compared to nab-pac alone.

Methods

Women w/ recurrent platinum-resistant/refractory high grade serous or endometroid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma w/ measurable or non-measurable disease and up to 4 chemotherapeutic regimens were 1:1:1 randomized to: -CONTINUOUS 100mg RELA daily (w/discretionary escalation to 150mg) + 80mg/m² nab-pac on days 1, 8, and 15 of a q28-day schedule; or -INTERMITTENT 150mg RELA the day before, of, and after 80mg/m² nab-pac on days 1, 8, and 15, of a q28-day schedule; or -COMPARATOR,100mg/m² nab-pac on days 1, 8, and 15, of a q28-day schedule. A lower nab-pac dose was used with RELA because RELA inhibits the metabolism of nab-pac. The primary endpoint was progression-free survival (PFS) determined by the investigator per RECIST 1.1.

Results

178 women were randomized. At median follow-up of 11.07 mos, the INTERMITTENT regimen significantly improved median PFS compared to nab-pac alone (HR, 0.66, 95%CI 0.44-0.98, log-rank test p=0.038). While ORR was similar, Duration of Response (DoR) was significantly improved (HR 0.36, 95% 0.16-0.77, p=0.006) in the INTERMITTENT regimen vs. nab-pac alone. Overall survival will be assessed at maturity. Most common grade ≥3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. Table: 721O

Conclusions

INTERMITTENT RELA + nab-pac improved PFS and had a favorable safety profile in recurrent platinum-resistant and/or platinum-refractory ovarian cancer patients.

Clinical trial identification

NCT03776812.

Editorial acknowledgement

Legal entity responsible for the study

Corcept Therapeutics.

Funding

Corcept Therapeutics.

Disclosure

N. Colombo: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Oncxe; Financial Interests, Personal, Speaker’s Bureau, Corcept Therapeutics: Novartis; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics. D.D. Nguyen: Financial Interests, Personal, Full or part-time Employment: Corcept Therapeutics. G.F. Fleming: Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Syros; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Principal Investigator: Iovance; Financial Interests, Personal, Principal Investigator: Sermonix; Financial Interests, Personal, Principal Investigator: Compugen; Financial Interests, Personal, Principal Investigator: Celldex; Financial Interests, Personal, Principal Investigator: Plexxicon; Financial Interests, Personal, Principal Investigator: AstraZeneca. R.N. Grisham: Financial Interests, Personal, Advisory Board: Signatera; Financial Interests, Personal, Advisory Board: Verastem; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: PER; Financial Interests, Personal, Advisory Board: Aptitude; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Principal Investigator: Context; Financial Interests, Personal, Principal Investigator: Verastem; Financial Interests, Personal, Principal Investigator: Bayer; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Novartis. D. Lorusso: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Other, Travel Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Principal Investigator: Clovis; Financial Interests, Personal, Principal Investigator: Corcept Therapeutics; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Other, Travel Grant: GSK; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Advisory Board: Pharmamar; Financial Interests, Personal, Principal Investigator: Immonogen; Financial Interests, Personal, Principal Investigator: Genmab; Financial Interests, Personal, Other, Travel Grant: Roche. T. Van Gorp: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: OncXerna; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Corcept Therapeutics. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Institutional, Principal Investigator: Abbvie Deutschland; Financial Interests, Institutional, Principal Investigator: Ability; Financial Interests, Institutional, Principal Investigator: Advaxis; Financial Interests, Institutional, Principal Investigator: Aeterna Zentaris. H.I. Pashova: Financial Interests, Personal, Full or part-time Employment: Corcept Therapeutics. A. Grauer: Financial Interests, Personal, Full or part-time Employment: Corcept Therapeutics.