(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Geoffrey B. Johnson, MD, PhD, discussing SECuRE, a dose escalation/expansion study to assess the anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with metastatic castrate resistant prostate cancer (mCRPC). Prostate cancer is common, and despite recent advances in treatment options, patients with metastatic disease still have poor outcomes. The double PSMA binding moiety of SAR-bisPSMA in 64Cu-SAR-bisPSMA (imaging) and 67Cu-SAR-bisPSMA (therapy) may offer advantages compared to currently used single-target PSMA agents:
Clinical evidence demonstrated 2-3 times higher uptake of 64Cu-SAR-bisPSMA compared to the single-target PSMA agent, 68Ga-PSMA-11. Additionally, pre-clinical efficacy data of 67Cu-SAR-bisPSMA in mice showed statistically significant tumor growth inhibition and increased survival in a prostate cancer xenograft study:
These results led to the development of the SECuRE trial, which aims to assess the safety and anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with mCRPC.
SECuRE is a Phase I/IIa multi-center, open-label, non-randomized, dose-escalation and cohort expansion study of 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA in patients with mCRPC. The target population is patients who have progressed despite having at least one androgen receptor pathway inhibitor and demonstrate positivity on 64Cu-SAR-bisPSMA PET. The study comprises 3 phases:
- Dosimetry (n = 6)
- Dose Escalation (n ~24)
- Cohort Expansion (n = 24)
The 67Cu-SAR-bisPSMA dose levels investigated in the dose escalation phase are: 4 GBq (cohort 1, single dose), 8 GBq (cohort 2, single dose), 12 GBq (cohort 3, single dose) and 24 GBq across two doses: cohort 4, two doses at the maximum tolerated dose or maximum feasible dose established in cohorts 1-3, and two additional doses may be offered in case of radiological non-progression:
Dose escalation has been completed, and the Safety Review Committee has recommended to proceed with the cohort expansion phase with 8 GBq of 67Cu-SAR-bisPSMA, with an increase in number of therapy cycles. The recently amended protocol will focus on the evaluation of mCRPC participants in the pre-chemotherapy setting and include a subset of patients who may also receive 67Cu-SAR-bisPSMA with enzalutamide.
The primary and key secondary objectives include assessment of 64Cu- and 67Cu-SAR-bisPSMA’s safety and dosimetry, and determining the anti-tumor efficacy of 67Cu-SAR-bisPSMA. Response to 67Cu-SAR-bisPSMA will be assessed biochemically (≥50% decline in PSA) and radiographically (by RECIST V1.1 and PCWG3). Enrollment of participants to the cohort expansion phase is ongoing at this time, with 5 sites in the United States currently enrolling participants:
ClinicalTrials.gov Identifier: NCT04868604.
Presented by: Geoffrey B. Johnson, MD, PhD, Mayo Clinic, Rochester, MN
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.