First-in-human phase 1 study of CC-94676, a first-in-class androgen receptor (AR) ligand-directed degrader (LDD), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

作者：Dana E. Rathkopf, Manish R. Patel, Atish D. Choudhury, Drew Rasco, Nehal J. Lakhani, Jessica E. Hawley, Ana M. Aparicio, Vivek Narayan, Sandy Srinivas, Karie Runcie, Hamid Emamekhoo, Zachery R. Reichert, Michael A. Carducci, Amber L. Wells, Can Liu, Raju Kandimalla, Jiaju Wu, Marie Huong Nguyen, Michael Pourdehnad, Andrew J. Armstrong · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.4_suppl.134 · 被引用次数：19 · 研究领域：Prostate Cancer Treatment and Research、Cancer Treatment and Pharmacology、Radiopharmaceutical Chemistry and Applications

134 Background: Androgen receptor (AR) signaling is the principal driver of PC at all stages. CC-94676 (BMS-986365) is a heterobifunctional, first-in-class, orally bioavailable AR LDD designed to induce rapid, sustained, and highly selective AR degradation in pts who progressed on standard of care therapies. We report initial results from an open-label, multicenter study, NCT04428788, evaluating CC-94676 in pts with progressive mCRPC. Methods: Pts with mCRPC who progressed on androgen deprivation therapy, ≥ 1 second generation hormonal therapy (eg, enzalutamide [enza], abiraterone [abi], darolutamide, and apalutamide) and taxane chemotherapy (chemo) (unless refused or not indicated) were enrolled to evaluate the safety, tolerability, PK/PD, and preliminary efficacy of CC-94676. Escalation doses evaluated were 100–1200 mg QD and 600–900 mg BID; expansion doses were 600 mg QD and 400–900 mg BID. Results: As of Aug 21, 2023, 95 pts received CC-94676 (median age 71 yrs) with a median of 5 (range 2–12) prior therapies, including enza (80%), abi (72%), both enza & abi (56%), and chemo (56%) (docetaxel 55%; cabazitaxel 20%). There were no ≥ Grade (G) 4 treatment-related adverse events (TRAEs) or discontinuations due to TRAEs. Of 27 pts treated in escalation, treatment (Tx) was well tolerated; 2 pts had non-serious G3 TRAEs at doses ≥ 800 mg QD, which were manageable with dose modifications. One dose-limiting toxicity of asymptomatic QTc prolongation was observed at 900 mg BID an...