biostudies-literatureRathkopf DEGlaxoSmithKlineDaiichi Sankyo EuropeU.S. Department of DefenseNCI NIH HHSProstate Cancer FoundationBristol-Myers Squibb Company76-88https://www.ebi.ac.uk/biostudies/studies/S-EPMC12094577biostudies-literatureUnknown36(1)<h4>Background</h4>Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC.<h4>Patients and methods</h4>Patients who progressed on androgen deprivation therapy, one or more ARPIs, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (part A) and expansion (part B) of BMS-986365 up to 900 mg twice daily. Primary objectives were safety and tolerability, and to define maximum toleratAnnals of oncology : official journal of the European Society for Medical OncologySafety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.PMC12094577P30 CA016672P30 CA008748P30 CA014236Wu JPourdehnad MEmamekhoo HArora VKKandimalla RRathkopf DEWells ALRuncie KDHawley JESuryawanshi SReichert ZRNarayan VPatel MRLakhani NLiu CHan JRasco DSrinivas SNguyen MHArmstrong AJChoudhury ADAparicio AfalseSafety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.<h4>Background</h4>Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC.<h4>Patients and methods</h4>Patients who progressed on androgen deprivation therapy, one or more ARPIs, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (part A) and expansion (part B) of BMS-986365 up to 900 mg twice daily. Primary objectives were safety and tolerability, and to define maximum tolerat2025-01-01T00:00:00Z2025 Jan2026-06-12T05:20:58.422Z2026-06-12T03:08:21.128ZS-EPMC120945773929351510.1016/j.annonc.2024.09.005