A Dose Escalation/Expansion Study to Assess the Anti-Tumor Efficacy of 67Cu-SAR-bisPSMA in Patients with Metastatic Castrate Resistant Prostate Cancer

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31^st and June 4^th, 2024 was host to a prostate, testicular, and penile cancers trials in progress poster session. Dr. Geoffrey Johnson presented SECuRE, a dose escalation/expansion study assessing the anti-tumor efficacy of ⁶⁷Cu-SAR-bisPSMA in patients with metastatic castrate-resistant prostate cancer (mCRPC).

Despite recent advances in prostate cancer treatment options, patients with metastatic disease still have poor outcomes, warranting the development of new effective therapies in this setting. Prostate-specific membrane antigen (PSMA) is expressed in benign and malignant prostate tissues and luminal surface of salivary/lacrimal glands, small intestine, and renal tubules. 

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 has demonstrated two to three-fold higher uptake of ⁶⁴Cu-SAR-bisPSMA compared to the single-target PSMA agents. Translational efficacy data of ⁶⁷Cu-SAR-bisPSMA in mice showed statistically significant tumor growth inhibition compared to the control group, as well as a dose-dependent delay in eventual tumor regression in a prostate cancer xenograft study. These results led to the development of this clinical study, which aims to assess the safety and anti-tumor efficacy of ⁶⁷Cu-SAR-bisPSMA in mCRPC patients.

SECuRE is a phase I/lla multi-center, open-label, non-randomized, dose-escalation and cohort expansion study of ⁶⁴Cu-SAR-bisPSMA and ⁶⁷Cu-SAR-bisPSMA. mCRPC patients with progression, prior exposure to ≥1 androgen receptor pathway inhibitor, and a positive ⁶⁴Cu-SAR-bisPSMA PET were eligible for treatment with ⁶⁷Cu-SAR-bisPSMA.

The primary and key secondary objectives include assessment of ⁶⁴Cu- and ⁶⁷Cu-SAR-bisPSMA safety and dosimetry, determining the maximum tolerated dose (MTD) or maximum feasible dose (MFD), and anti-tumor efficacy of ⁶⁷Cu-SAR-bisPSMA. Radiological response will be assessed via RECIST v1.1 and PCWG3 criteria.
This study is being conducted in 3 phases:

• ⁶⁴Cu-SAR-bisPSMA Dosimetry Phase (n=6)
• ⁶⁷Cu-SAR-bisPSMA Dose Escalation Phase (n=up to 24)
• ⁶⁷Cu-SAR-bisPSMA Cohort Expansion Phase (n=14)

The full eligibility criteria are summarized below:

At the time of presentation, no dose-limiting toxicities had been observed to date in cohorts 1, 2, and the first three patients enrolled in cohort 3. In the United States, four sites are active with additional sites in planning. Additional sites in the US and Australia are currently in start-up.

Presented by: Geoffrey Johnson, MD, PhD, Associate Professor of Radiology, Mayo Clinic, Rochester, MN

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 Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, May 31^st – June 4^th, 2024