Intraprostatic enzalutamide implants show feasibility for localized prostate cancer

Initial findings from a phase 1 study (NCT06257693) suggest that intraprostatic delivery of enzalutamide (Xtandi) via a sustained-release implant may achieve high local drug concentrations with minimal systemic exposure in men with localized prostate cancer undergoing prostatectomy.

The approach, which aims to localize androgen receptor inhibition within the prostate, demonstrated a favorable safety profile and early signals of tumor volume reduction on imaging. The results were presented by Braden Millan, MD, MSc, FRCSC, urologic oncology fellow at the National Cancer Institute, at the 41st Annual European Association of Urology Congress in London, United Kingdom.

“The preliminary safety and efficacy data from this study are compelling and demonstrate the potential of Enolen to serve as a new treatment option for men with localized prostate cancer that avoids the negative [adverse] effects of current treatments,” said principal investigator Peter Pinto, MD, chief of the Prostate Cancer Division at the National Cancer Institute, in a news release.² “These initial findings, particularly MRI-documented tumor shrinkage and therapeutic enzalutamide levels in the prostate with minimal systemic exposure, strongly support further development of Enolen.”

The investigational Enolen platform seeks to repurpose enzalutamide for localized delivery. According to the study investigators, the implant enables sustained drug release directly within the prostate, potentially achieving therapeutic concentrations in tumor tissue while limiting systemic exposure. The agent was granted fast track designation in January 2026.³

The ongoing phase 1 study of Enolen is evaluating the safety, feasibility, and pharmacokinetics of the intraprostatic enzalutamide implants in men with localized prostate cancer prior to planned prostatectomy. The implants consist of enzalutamide embedded within a nonbiodegradable polymer matrix and are placed directly into MRI-visible lesions using a transperineal approach. Implants were left in situ for approximately 3 to 12 weeks, followed by repeat MRI and subsequent prostatectomy. In total, 20 patients enrolled in the initial cohort were successfully implanted. Particapants received an average of 12 implants (range, 7 to 16).

Across all patients, there were no grade 3 or higher treatment-related adverse events attributed to the implant procedure, and no grade 2 or higher toxicities were attributed to the implants themselves. No new safety concerns related to surgery were identified. Further, there were no reported effects on testosterone levels or negative effects on sexual function.

Pharmacokinetic analyses demonstrated low systemic exposure, with serum enzalutamide levels remaining below the inhibitory concentration (IC50). In contrast, intraprostatic tissue concentrations were highest near the implant and remained above the IC50 even at distances up to 15 mm.

From an imaging standpoint, 29 of 31 evaluable lesions showed either stability or reduction in tumor volume on MRI. According to the sponsor-reported data,² tumor volume reduction was observed in 84% of lesions over an average duration of 35 days. There were no delays to surgery among any patients in the cohort.

The investigators reported that accrual for the initial cohort has been completed, with additional cohorts now enrolling to evaluate different dose levels and implant durations.

“Being the first study to demonstrate that enzalutamide can be safely and locally administered to the prostate via sustained drug eluting implants is a significant clinical milestone both for Alessa and for the broader treatment landscape for prostate cancer,” said Pamela Munster, MD, Chief Scientific Advisor and founder of Alessa, in the news release.² “We look forward to continuing our clinical advancement of Enolen, which includes further investigation of dose optimization and duration of drug exposure through two additional cohorts underway in this phase 1 trial.”

REFERENCES
1. Millan B, Gurram S, Turkbey B, et al. A phase 1 safety, PK and preliminary efficacy study of localized therapy using Enolen® (Enzalutamide) implants for early-stage prostate cancer. Presented at: 41st Annual Congress of the European Association of Urology. London, UK. March 13-16, 2026. Abstract A0601

2. Alessa Therapeutics announces positive preliminary safety and efficacy data from Enolen phase 1 trial. News release. Alessa Therapeutics. March 16, 2026. Accessed March 18, 2026. https://alessatherapeutics.com/news/alessa-therapeutics-announces-positive-preliminary-safety-and-efficacy-data-from-enolen-phase-1-trial/

3. Alessa Therapeutics announces FDA fast track designation for Enolen, a first-of-its-kind treatment for localized prostate cancer. News release. Alessa Therapeutics. January 8, 2026. Accessed March 18, 2026. https://alessatherapeutics.com/news/alessa-therapeutics-announces-fda-fast-track-designation-for-enolen-a-first-of-its-kind-treatment-for-localized-prostate-cancer/