Phase 2 study of ASP5541 (PRL-02), a long-acting intramuscular depot injection of abiraterone decanoate, in patients with advanced prostate cancer.

TPS300 Background: Globally, prostate cancer (PC) is the second most diagnosed cancer in men and fifth leading cause of cancer death. Patients (pts) with advanced PC have limited treatment options. While abiraterone acetate (AA) improves survival in pts with metastatic hormone-sensitive PC (mHSPC) and metastatic castration-resistant PC (mCRPC), it has low oral bioavailability and a risk of hepato- and mineralocorticoid toxicity. ASP5541 is a long-acting intramuscular (IM) depot injection of abiraterone decanoate that delivers abiraterone to target tissues and lymphatics, reducing systemic exposure. This, and its unique pharmacokinetics, may reduce the need for glucocorticoids, lower mineralocorticoid toxicity, and decrease treatment burden. A Phase 1 study of ASP5541 (NCT04729114) in pts with advanced PC established 1260mg every 12 weeks (Q12W) as the recommended Phase 2 dose based on safety, pharmacodynamics (PD), and efficacy data. This Phase 2 study aims to evaluate the efficacy and safety of ASP5541 (± prednisone [pred]) vs AA in pts with advanced PC. Methods: This randomized, Phase 2 study (NCT07005154) plans to enroll ~218 adults with PC across 3 cohorts. Inclusion criteria are histologically/cytologically confirmed metastatic PC with ECOG PS 0/1 (2 if due to bone pain); and baseline serum testosterone <50ng/dL (for mCRPC). Eligible adults will have received androgen-deprivation therapy (ADT), consisting of prior bilateral orchiectomy or concurrent gonadotropin-releasing hormone agonist or antagonist therapy, plus a cohort-specific regimen (Table). In Cohort 2, ASP5541 will be administered without pred. Primary endpoints are shown in the Table. Secondary endpoints for all cohorts are radiographic progression-free survival; PSA50; time to PSA progression, objective response rate, duration of response, best overall response, PSA undetectable rate at ≤0.02ng/mL for all cohorts and at ≤0.2ng /mL for Cohorts 1 and 3 only; PSA90 (Cohorts 2, 3); safety, PD, and time-to-pain progression. Recruitment is planned across the Americas, Europe, and the Asia-Pacific region. Clinical trial information: NCT07005154 . Cohorts Indications Randomization N Treatment Primary endpoints 1 Androgen receptor pathway inhibitor (ARPI)-naïve mCRPC 1:1 50 per group Group A: ASP5541 + pred + ADT; Group B: AA + pred + ADT Proportion of pts with PSA90 2 ARPI-naïve mHSPC 1:1 (for Groups B and C) 10 for Group A; 50 for Group B and 50 for Group C Group A (safety run-in): ASP5541 + ADT (steroid free); Group B: ASP5541 + ADT (steroid free); Group C: AA + pred + ADT Group A: rates of no mineralocorticoid toxicity (grade ≥1 hypokalemia or grade ≥2 hypertension)Group B and C: proportion of pts with PSA ≤0.2 ng/mL at 8 months 3 mCRPC or mHSPC(Japanese pts) N/A 3–8 ASP5541 + pred + ADT Safety ASP5541 1260 mg IM once every 12 weeks (Q12W); AA 1000 mg orally (PO) once daily (QD); pred PO 5 mg twice daily for mCRPC and 5 mg QD for mHSPC.