AUA 2024: Phase II Study of Neoadjuvant Lu-177-PSMA-617 in Patients with High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy (PRELUDE Trial)

(UroToday.com) The 2024 American Urological Association (AUA) Annual Meeting held in San Antonio, TX between May 3^rd and 6^th, 2024 was host to a cancer clinical trials in progress session. Dr. Nitin Yerram presented the PRELUDE trial, a phase II study of neoadjuvant ¹⁷⁷Lu-PSMA-617 in patients with high-risk, localized prostate cancer undergoing a radical prostatectomy.

The ideal management of clinically localized high-risk prostate cancer patients remains a challenge given the high likelihood of biochemical failure following radical therapy. Randomized trials of neoadjuvant therapy have demonstrated improved pathologic outcomes; however, there appears to be limited long-term benefit with regard to oncologic efficacy outcomes. PSMA has emerged as an actionable target for molecular imaging and theranostics, with ¹⁷⁷Lu-PSMA-617 currently approved for metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with a taxane chemotherapy and androgen receptor pathway inhibitor based on the results of two major trials in this space: VISION and TheraP.^1,2

PRELUDE is an open-label phase II trial evaluating the use of neoadjuvant ¹⁷⁷Lu-PSMA-617 in patients with high-risk, localized prostate cancer undergoing a radical prostatectomy. Eligible patients include those meeting the following criteria:

Gleason Score ≥ 8
PSMA-defined prostate-only disease
- No lymph node involvement
- No distant metastases
Patient desiring a radical prostatectomy

In this trial, patients will receive two cycles of ¹⁷⁷Lu-PSMA-617 six weeks apart (weeks 0 and 6), followed by an interval, pre-operative PSMA PET/CT at week 11 to assess treatment response. Following surgery, patients will undergo post-operative surveillance with PSA testing, correlative studies, and quality-of-life assessment (EPIC-26 Quality-of-life and sexual function changes questionnaire) every three months.

The study endpoints are as follows:

Primary: Prostate cancer downstaging
- Complete downstaging: No visible tumor in the surgical sample
- Very good response: Downstaging from high-risk disease (Grade Group ≥4) to low-risk pathologic disease (Grade Group 1 disease)
- Good response: Downstaging from high-risk disease (Grade Group ≥4) to intermediate-risk pathologic disease (Grade Group 2 or 3 disease)

Secondary endpoints include:
- Change in PSMA-avid tumor load
- Safety of radical prostatectomy following 2 cycles of ¹⁷⁷Lu-PSMA-617
- Quality of life and sexual function changes
- 2-year biochemical recurrence rate
Exploratory endpoints
- Circulating prostatsome/extracellular vesicles and miRNA levels

The target sample size is 54 patients. This trial will follow a two-stage sequential design, whereby 2/27 patients in the first phase will be required to exhibit downstaging to continue the trial without modification. This trial is currently enrolling at two sites: Hackensack University Medical Center and Georgetown University Medical Center.

Presented by: Nitin Yerram, MD, Co-Director of Urologic Oncology, Director of Urologic Research at Hackensack University Medical Center, Hackensack, NJ

Written by: Rashid Sayyid, MD, MSc - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, May 3^rd - 6^th, 2024

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