Onapristone (ONA) in progesterone receptor (PR)-expressing tumors: Efficacy and biomarker results of a dose-escalation phase 1 study.

5593 Background: ONA is a type I PR antagonist, which prevents PR-induced DNA transcription. Immediate release (IR) 100 mg ONA was active in multiple preclinical models and in patients (pts) with breast cancer (BC). We conducted a phase 1 study of extended release (ER) ONA to (i) determine a recommended dose and (ii) explore the role of transcriptionally-activated PR (APR), detected as an aggregated subnuclear distribution pattern, as a predictive immunohistochemical (IHC) biomarker. Methods: An open-label, multicenter, randomized, parallel-group, phase 1 study (target n=48; NCT02052128) included female pts ≥18 years with PRpostumors. APR analysis was performed on archival tumor tissue. Pts were randomized to 5 cohorts of ER ONA tablets 10-50 mg BID, or IR 100 mg QD until progressive disease or intolerability. This abstract reports the APR IHC analysis and clinical benefit (PR/SD≥24 wks). Results: Phase 1 is complete (n=52). Tumors (n) were: endometrial carcinoma (EC) 13; breast cancer (BC) 20; ovarian ca...