biostudies-literatureAbida WNational Cancer InstituteNCI NIH HHS1111-1120https://www.ebi.ac.uk/biostudies/studies/S-EPMC10947849biostudies-literatureUnknown30(6)<h4>Purpose</h4>Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.<h4>Patients and methods</h4>Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase 2 dose (RP2D).<h4>Results</h4>A tClinical cancer research : an official journal of the American Association for Cancer ResearchPhase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide.PMC10947849P30 CA008748P30-CA008748Agarwal NWang AMultani PSHahn AWRettig MXu RLogothetis CJSmith MRSieber PWang JChow Maneval EJunttila MRBarkund SPankov AMorris MJDorff TDuff MShore NPatel RAbida WPage ADaemen AMonk PfalsePhase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide.<h4>Purpose</h4>Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.<h4>Patients and methods</h4>Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase 2 dose (RP2D).<h4>Results</h4>A t2024-01-01T00:00:00Z2024 Mar2026-06-02T04:58:06.246Z2025-04-04T02:04:57.451ZS-EPMC109478493822695810.1158/1078-0432.ccr-23-350810.1158/1078-0432.CCR-23-3508