(UroToday.com) The 2025 European Society for Medical Oncology (ESMO) Annual Congress, held in Berlin, Germany, was host to a prostate cancer poster session. Dr. Jose Avitia presented the results of a phase I trial of ASP5541 (PRL-02), a long-acting intramuscular depot injection of abiraterone decanoate in patients with advanced prostate cancer.
Prostate cancer is the most common cancer in men in the United States, with an estimated 313,780 new cases and 35,770 deaths in 2025.1 Abiraterone acetate (AA), a prodrug of the active moiety abiraterone that inhibits CYP17, improves survival in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancers (mCRPC). However, AA requires concomitant glucocorticoids to prevent mineralocorticoid-related toxicity and is associated with a risk of hepatotoxicity.
ASP5541 is a long-acting intramuscular (IM) depot injection of abiraterone decanoate, a novel prodrug of abiraterone, that enables efficient delivery of abiraterone to the lymphatic system and other target tissues (prostate, testes, and adrenal glands) while minimizing plasma and liver exposure. The differentiated pharmacokinetic (PK) properties of ASP5541, including low systemic exposure of abiraterone, may decrease the need for concomitant glucocorticoids, minimize drug-drug interactions, and lead to an overall improved safety profile compared to oral AA.
This phase I open-label study (NCT04729114) included adults with mHSPC or mCRPC, testosterone < 50 ng/dL, and Eastern Cooperative Oncology Group performance status score of 0 or 1 (Figure 1). Of note, prior androgen receptor pathway inhibitors (ARPIs) were permitted during the dose escalation portion and were required for dose expansion.
ASP5541 was administered by IM injection every 84 days at doses ranging from 180–1,800 mg during dose escalation (Cohorts 1–5), and at 1,260 mg for dose expansion (Cohorts D and E), plus oral glucocorticoids once daily. The primary endpoints were determination of the
- Recommended Phase 2 dose (RP2D)
- Safety
- Testosterone suppression to ≤ 1 ng/dL
The secondary endpoints were PK and efficacy.
Interim analysis data presented by Dr. Avitia included patients who completed 1 cycle of
ASP5541 or discontinued before the end of the first cycle. The categorical variables were summarized using frequencies and percentages. Continuous variables were summarized using descriptive statistics.
At the interim analysis (data cutoff : January 31, 2025), 68 patients were included, of which 14 had mHSPC and 54 had mCRPC (including 8 with ARPI-naïve mCRPC). From a pharmacokinetics standpoint, abiraterone exposure increased dose-proportionally following ASP5541 administration. The average steady-state abiraterone concentration following ASP5541 1,260 mg was approximately 2.5 ng/ml, with a half-life of ~25 days. The average steady state abiraterone concentration was ~13 times greater with AA than with 1,260 mg ASP5541 (~33.33 ng/ml for AA vs ~2.5 ng/ml for ASP5541 1,260 mg).
Testosterone suppression showed an exposure–response relationship (Figure 3A and 3B) – At the RP2D of 1,260 mg, suppression to ≤ 1 ng/dL was achieved by 43/48 (90%) patients by cycle 1 day 28. A trend was observed suggesting that increased abiraterone exposure is associated with a higher probability of elevations in progesterone and corticosterone levels.
At the data cut-off, 26 patients in the dose escalation cohorts were included in the interim
analysis set for efficacy. Reductions in serum prostate-specific antigen (PSA) levels were observed from doses ≥ 720 mg, with confirmed PSA50 responses from baseline observed in 5/6 (83.3%) patients at 1,260 mg.
In the prior ARPI mCRPC dose expansion cohorts (Cohort D and Cohort E), the confirmed PSA50 response rates were 2/18 (11.1%) and 3/24 (12.5%), respectively. Among the 8 ARPI-naïve patients with mCRPC, all patients achieved a confirmed PSA50 response, and 7 (87.5%) had confirmed PSA90 response from baseline (1/2 at 720 mg, 4/4 at 1,260 mg, and 2/2 at 1,800 mg). The median treatment duration was 2.4 years, and 6 (75%) patients remained on treatment at data cut-off.
Across all doses, there were no dose-limiting toxicities or adverse events (AEs)
leading to discontinuation (Table 1). The safety events were generally low grade and manageable. Treatment-related AEs (TRAEs) occurred in 43/68 (63.2%) patients. The most
common TRAEs were:
- Fatigue (16.2%)
- Injection site reaction (16.2%)
- Injection site pain (14.7%)
- Contusion (8.8%)
- Hot flush (7.4%)
- Hypertension (7.4%)
2/68 (2.9%) patients experienced a treatment-related serious AE – 1 patient each had upper gastrointestinal hemorrhage and enlarging aortic aneurysm. One patient experienced a treatment emergent AE (TEAE) of cardiac arrest leading to death that was not considered related to treatment
No significant liver toxicity was reported. Increased alanine and aspartate transaminase levels were reported in 3/68 patients (4.4%) and 1/68 (1.5%), respectively; all events were grade ≤2 in severity. The rates of mineralocorticoid toxicity were low – at the RP2D of 1,260 mg, new grade ≥ 2 hypertension occurred in 6/48 (12.5%) and any-grade hypokalemia occurred in 3/48 (6.3%) patients. Notably, no meaningful differences in frequency, type, or severity of TEAEs were reported across doses or cohorts
Dr. Avitia concluded as follows:
- Based on safety, efficacy, and PK/PD data, the RP2D for ASP5541 is determined as 1,260 mg IM every 84 days
- ASP5541 showed a highly differentiated PK profile, with low systemic abiraterone exposure compared with AA.
- ASP5541 was highly effective at suppressing testosterone, with 90% of patients achieving testosterone ≤ 1 ng/dL at the RP2D of 1,260 mg
- ASP5541 showed encouraging efficacy with deep and durable PSA responses in ARPI-naïve patients with mCRPC
- 100% (8/8) patients achieved a confirmed PSA50 response and 87.5% (7/8) had confirmed PSA90 from baseline
- ASP5541 was well-tolerated, with low rates of mineralocorticoid toxicity and no clinically significant liver toxicity observed
- ASP5541 will be further evaluated in a phase II study (NCT07005154) with and without concomitant glucocorticoids
Presented by: Jose Avitia, MD, Medical Oncologist, New Mexico Cancer Center, Albuquerque, New Mexico
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center – Tucson, AZ, @rksayyid on X during the 2025 European Society of Medical Oncology (ESMO) Annual Congress held in Berlin, Germany, between September 17th and 21st.
References:
- Key Statistics for Prostate Cancer. American Cancer Society 2024. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html. Accessed September 10, 2025