Mp14-19 Arv-766, a Protac Androgen Receptor (Ar) Degrader, Combined With Abiraterone in Novel Hormonal Agent (Nha)-Nave Metastatic Prostate Cancer: Phase 1 Cohort (Part C) of a Phase 1/2 Study

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP14)1 May 2024MP14-19 ARV-766, A PROTAC ANDROGEN RECEPTOR (AR) DEGRADER, COMBINED WITH ABIRATERONE IN NOVEL HORMONAL AGENT (NHA)-NAÏVE METASTATIC PROSTATE CANCER: PHASE 1 COHORT (PART C) OF A PHASE 1/2 STUDY Neal Shore, Joshua M. Lang, Daniel M. Geynisman, Tyler F. Stewart, Xin Gao, Leonard J. Appleman, Robert Dreicer, Tanya Dorff, Elmer Berghorn, Elizabeth Duperret, Haolan Lu, Edward Chan, Benjamin Garmezy, and Daniel P. Petrylak Neal ShoreNeal Shore , Joshua M. LangJoshua M. Lang , Daniel M. GeynismanDaniel M. Geynisman , Tyler F. StewartTyler F. Stewart , Xin GaoXin Gao , Leonard J. ApplemanLeonard J. Appleman , Robert DreicerRobert Dreicer , Tanya DorffTanya Dorff , Elmer BerghornElmer Berghorn , Elizabeth DuperretElizabeth Duperret , Haolan LuHaolan Lu , Edward ChanEdward Chan , Benjamin GarmezyBenjamin Garmezy , and Daniel P. PetrylakDaniel P. Petrylak View All Author Informationhttps://doi.org/10.1097/01.JU.0001009428.69695.82.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: ARV-766 is a second-generation PROteolysis TArgeting Chimera (PROTAC) AR degrader that targets wild-type AR and clinically relevant mutants. Parts A target n=150). In part A (dose escalation), patients (pts) who had ≥2 prior therapies (including ≥1 NHA) were given ARV-766 orally once daily (QD) in ascending doses to assess safety and tolerability and select recommended phase 2 doses (RP2Ds); in part B (cohort expansion), pts treated with 1–3 prior NHAs and ≤2 chemotherapy regimens were randomized to receive 100 mg or 300 mg ARV-766 orally QD to evaluate the antitumor activity of the RP2Ds. The NHA abiraterone is approved for pts with mCRPC or high-risk metastatic castration-sensitive prostate cancer (mCSPC). Combining drugs that target different steps of the AR signaling pathway may yield a synergistic treatment effect. Part C of this study will assess the addition of ARV-766 to abiraterone for the treatment of NHA-naïve mCRPC or mCSPC. METHODS: Part C will enroll ≤24 men (aged ≥18 y) with histologically, pathologically, or cytologically confirmed mCRPC or mCSPC, Eastern Cooperative Oncology Group performance status score of 0 or 1, and no prior NHA treatment. Pts will receive escalating doses of ARV-766 (starting at 100 mg QD) with standard-dose abiraterone to assess drug-drug interaction (DDI) and safety of the combination; pts will also receive androgen deprivation therapy of choice. Dose escalation will follow a conventional 3+3 cohort design based on safety and abiraterone pharmacokinetics. The primary endpoints of part C are first-cycle dose-limiting toxicities and frequency and severity of adverse events (AEs) and laboratory abnormalities. RESULTS: As of August 23, 2023, 84 pts with mCRPC received ARV-766 monotherapy in parts A 2% grade 3), nausea (14%; 0 grade 3), diarrhea (11%; 1% grade 3), vomiting (11%, 0 grade 3), decreased appetite (11%, 0 grade 3), and alopecia (10%). There were no grade ≥4 TRAEs with ARV-766 monotherapy; 3 pts had TRAEs leading to ARV-766 discontinuation. CONCLUSIONS: ARV-766 monotherapy was well tolerated in NHA-exposed pts with mCRPC; analyses of anti-tumor activity in parts A & B are ongoing. Part C of the study will assess the safety, tolerability, and DDI of combination ARV-766/abiraterone treatment in NHA-naïve mCRPC or mCSPC. Source of Funding: This study is sponsored by Arvinas Androgen Receptor, Inc © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e227 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Neal Shore More articles by this author Joshua M. Lang More articles by this author Daniel M. Geynisman More articles by this author Tyler F. Stewart More articles by this author Xin Gao More articles by this author Leonard J. Appleman More articles by this author Robert Dreicer More articles by this author Tanya Dorff More articles by this author Elmer Berghorn More articles by this author Elizabeth Duperret More articles by this author Haolan Lu More articles by this author Edward Chan More articles by this author Benjamin Garmezy More articles by this author Daniel P. Petrylak More articles by this author Expand All Advertisement PDF downloadLoading ...