Phase 2 clinical study of onapristone (ONA) in patients (pts) with uterine endometrioid adenocarcinoma (EC) expressing the activated progesterone receptor (APRpos).

TPS5616 Background: ONA is a type I PR antagonist, which prevents PR-induced DNA transcription. Presence of transcriptionally-activated PR (APR), seen as an aggregated subnuclear PR distribution pattern, is being explored as a predictive biomarker for ONA activity. The proposed IHC companion diagnostic could select pts with uterine EC most likely to respond to ONA. An extended-release (ER) formulation has been developed to provide constant target exposure to the anti-progestin and address previously-observed liver function test abnormalities. ONA anti-cancer activity has been documented in multiple preclinical models. Pts with APRpos EC, breast and ovarian cancers have experienced clinical benefit (PR or SD ≥ 6 months) on ONA, with excellent tolerability. The current study was designed to test the hypothesis that the APR companion diagnostic identifies the pts most likely to respond to ONA, with 80% power to detect a response rate of 30%. Methods: This is an ongoing multi-center, open-label, randomized, p...