ASCO 2023: Phase 1/2a Study of PRL-02, a Long-Acting Intramuscular Depot Injection of Abiraterone Decanoate, in Patients with Advanced Prostate Cancer

( The 2023 ASCO annual meeting included a prostate cancer session, featuring a trials-in-progress presentation by Dr. Neal Shore discussing a phase 1/2a study of PRL-02, a long-acting intramuscular depot injection of abiraterone decanoate, in patients with advanced prostate cancer. PRL-02 is a long-acting intramuscular 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.

For this trial, phase 1 is a standard 3+3 design intended to identify a recommended Phase 2 dose. PRL-02 is administered every 84 days (1 cycle). As of September 8, 2022, 17 patients (6 mCRPC, 11 mCSPC) were treated across 5 dose cohorts (180, 360, 720, 1260, 1800mg). At 720mg and above, 13 of 16 had a 90% reduction in testosterone, including 2 patients with testosterone ≤ Lower Limit of Quantitation of 0.1 ng/dL. The median baseline PSA was 3.01 ng/mL, with a PSA decline of ≥50% from baseline was observed in 15 of 16 patients and a PSA decline of ≥90% from baseline observed in 8 of 16 patients. 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 recommended Phase 2 dose) and lower.

The Phase 1 dose expansion will include two dose expansion groups of up to 12 patients and each is planned at the recommended Phase 2 dose: Group A (prior abiraterone) and Group B (prior second generation non-steroidal antiandrogen, ie. enzalutamide, apalutamide, and/or darolutamide). Groups A and B will enroll patients with mCRPC with previous orchiectomy or receiving concurrent GnRH agonist or antagonist therapy. PSA progression required as >=2 occurrences of rising PSA >= 1 week apart and a PSA concentration of >2 ng/mL at screening if confirmed PSA rise is the only measure of progression, and /or worsening measurable disease on CT/MRI per RECIST v1.1 criteria and/or >=1 new documented lesion on a bone scan. Patients in both groups will receive PRL-02 in combination with dexamethasone. The intention of this phase 1 dose expansion cohort is to characterize preliminary safety and efficacy in these patient populations.

Phase 2a of this trial is an A'Hern single-stage design. The objective is to evaluate the preliminary efficacy of PRL-02 in patients with mCSPC and mCRPC. Group 1 includes patients with mCSPC divided into 2 groups: Group 1A - previously untreated high-volume disease and Group 1B - previously untreated, low-volume disease. Group 2 includes patients with mCRPC. Enrollment for phase 2a is planned for 109 patients across 30 sites in the U.S. (NCT04729114). The following table summarizes the patient population, treatment, primary endpoints, hypothesis testing and rationale of the PRL-02 phase 2a trial:

PRL-02 phase 2a trial.jpg

Presented by: Neal D. Shore, MD, Carolina Urologic Research Center, Myrtle Beach, SC

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.