Phase 1/2a study of PRL-02, a long-acting intramuscular (IM) depot injection of abiraterone decanoate, in patients (pts) with advanced prostate cancer.

person Neal D. Shore Carolina Urologic Research Center, Myrtle Beach, SC info_outline Neal D. Shore, Jose W. Avitia, James L. Bailen, Luke T. Nordquist, William Richardson, Cody J. Peer, William Douglas Figg, Jacqueline M. Walling, Joel Robert Eisner, Matthew Sharp, Robert J. Schotzinger, William R. Moore, Ronald F. Tutrone

Authors person Neal D. Shore Carolina Urologic Research Center, Myrtle Beach, SC info_outline Neal D. Shore, Jose W. Avitia, James L. Bailen, Luke T. Nordquist, William Richardson, Cody J. Peer, William Douglas Figg, Jacqueline M. Walling, Joel Robert Eisner, Matthew Sharp, Robert J. Schotzinger, William R. Moore, Ronald F. Tutrone Organizations Carolina Urologic Research Center, Myrtle Beach, SC, Oncology Hematology Consultants Ltd., Albuquerque, NM, First Urology, Jeffersonville, IN, Urology Cancer Center, PC, Omaha, NE, National Cancer Institute, Bethesda, MD, Propella Therapeutics, Inc., Pittsboro, NC, Consultant, Chapel Hill, NC, Propella Therapeutics, Inc, Pittsboro, NC, Chesapeake Urologic Research Associates, Towson, MD Abstract Disclosures Research Funding U.S. National Institutes of Health U.S. National Institutes of Health, Propella Therapeutics,Inc Background: PRL-02 is a long-acting IM depot injection of abiraterone decanoate, a novel prodrug of abiraterone delivered through the lymphatic system. PRL-02 potently blocks androgen production with minimal increases in mineralocorticoids or decreases in glucocorticoids through preferential inhibition of Cytochrome P450 (CYP)17 lyase versus CYP17 hydroxylase. Phase 1 is a standard 3+3 design intended to identify a recommended Phase 2 dose (RP2D). PRL-02 is administered every 84 days (1 cycle). As of 9/8/22, 17 pts (6 mCRPC, 11 mCSPC) were treated across 5 dose cohorts (180, 360, 720, 1260, 1800mg). At 720mg and above, 9 of 11 had a 90% reduction in testosterone (T), including 2 pts with T≤ Lower Limit of Quantitation (LLOQ) of 0.1ng/dL. A PSA decline of ≥50% from baseline (PSA50) was observed in 8 of 10pts. PRL-02 was very well tolerated. Only minimal and transient changes in ‘upstream’ steroids (e.g., progesterone) were observed at doses of 1260 mg (the RP2D) and lower. Methods: Phase 2a is an A'Hern single-stage design. Group 1 includes pts with mCSPC divided into 2 groups (1A: previously untreated high-volume disease and 1B: previously untreated, low-volume disease). Group 2 includes pts with mCRPC. Enrollment of 66 pts is planned across 30 sites in the U.S. (NCT04729114). Patient populations, interventions and study design are described below. Clinical trial information: Clinical Trial information: NCT04729114 . Patient population, primary endpoints, hypothesis testing and rationale. Group 1A 1B 2 Patient Population mCSPC, previously untreated high-volume disease mCSPC, previously untreated, low-volume disease Chemotherapy-naïve, mCRPC Treatment PRL-02 + dexamethasone (Dex) + docetaxel +Androgen Deprivation Therapy (ADT) PRL02 + Dex + ADT PRL02 + Dex + ADT Primary Endpoint Undetectable PSA (≤0.2ng/mL) at 8 months Undetectable PSA (≤0.2ng/mL) at any time PSA50 confirmed by a second consecutive PSA at least 3 weeks later H0 and Ha 0.51, 0.70 0.51, 0.70 0.50, 0.75 Rationale/ Precedent PEACE-1 trial (NCT01957436) (Mescam 2022; Klaassen 2022), which showed a strong correlation between undetectable PSA at 8 months and clinical benefit. (overall survival and Radiographic progression-free survival) The combination of abiraterone + prednisone + docetaxel + ADT had a 51% rate of undetectable PSA at months Null hypothesis based on the LATITUDE study (NCT01715285) (Fizazi 2019; Tran 2019) in which the undetectable PSA rate at any time was 0.55 Null hypothesis based on the activity of the ACIS study control arm abiraterone + prednisone (NCT02257736) (Saad 2021)