67Cu-SAR-bisPSMA Earns FDA Fast Track Designation for PSMA+ mCRPC

The FDA has granted fast track designation to 67Cu-SAR-bisPSMA for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with androgen receptor pathway inhibition (ARPI).1

The designation was based on preliminary data from the phase 1/2a SECuRE trial (NCT04868604), which showed that 73% of evaluable patients treated across all dose-escalation cohorts experienced reductions in PSA levels. Forty-five percent of patients achieved PSA reductions of more than 50%, including some patients who received only 1 dose of 67Cu-SAR-bisPSMA at 4, 8, or 12 GBq.

Patients in cohorts 2, 3, and 4 received the agent at a single 8-GBq dose, a single 12-GBq dose, and a 12-GBq multi-dose, respectively; in this population, PSA reductions of more than 35% occurred in nearly 75% of patients, and nearly half achieved PSA reductions of at least 80%.

No dose-limiting toxicities were reported in the study’s first 3 cohorts (n = 15). Treatment-related adverse effects (AEs) were primarily grade 1 or 2, and the most common AE was grade 1 dry mouth (33.3%).

Previously, the FDA granted 2 fast track designations to the diagnostic 64Cu-SAR-bisPSMA for use in patients with suspected metastasis of prostate cancer who are candidates for initial definitive therapy; and for patients with biochemical recurrence of prostate cancer following definitive therapy.

"Receiving 3 fast track designations for the 1 molecule, SAR-bisPSMA, within the last 6 months is an incredible achievement for Clarity, highlighting how impressive our science and development are, the significance of the diagnostic and therapeutic data so far, and the high unmet need for better therapies and diagnostics in prostate cancer,” Alan Taylor, PhD, executive chairperson of Clarity Pharmaceuticals, stated in a news release. “The dual-targeted bisPSMA molecule was developed at the benchtop of Australian science with the intent of overcoming the shortfalls of the current generation of PSMA-targeting products. It was optimized with 2 PSMA ligands, which increases not only the amount of product in the lesions, but also how long the product is retained in the lesions over time, making it an ideal candidate for both diagnosis and therapy. The clinical data in both diagnostic and therapeutic indications that we are generating is remarkable, confirming the results that we initially saw in preclinical development.”

The SECuRE trial is an open-label, nonrandomized study enrolling patients at least 18 years of age with mCRPC with documented disease progression who received prior treatment with androgen deprivation therapy and at least 1 ARPI.2 A positive 64Cu-SAR-bisPSMA PET/CT scan is also required. Other key inclusion criteria consist of an ECOG performance status of 0 to 2; a life expectancy of more than 6 months; at least 1 metastatic lesion; and adequate organ function.

Patients are being excluded if they have brain metastases; a histologic diagnosis of small cell or neuroendocrine prostate cancer; a prior history of leukemia or myelodysplastic syndrome; or deep vein thrombosis or pulmonary embolism within 4 weeks of enrollment.

In the dose-escalation portion of the study, patients are receiving up to 2 administrations of 67Cu-SAR-bisPSMA; during cohort expansion, 2 doses will be given at the recommended dose level identified via dose escalation.

The study’s primary end points are the biodistribution and dosimetry of 64Cu-SAR-bisPSMA; to determine the maximum tolerated dose and recommended phase 2 dose of 67Cu-SAR-bisPSMA; and preliminary efficacy.

Enrollment for cohort 4 is complete; 3 patients from this group received 2 doses of study treatment and are in safety and efficacy follow-up.1 After the follow-up period, a safety review committee meeting is expected to be held in March 2025.

References

1. Clarity receives US FDA fast track designation for the treatment of metastatic castration-resistant prostate cancer patients with Cu-67 SAR-bisPSMA. News release. Clarity Pharmaceuticals. February 19, 2025. Accessed February 19, 2025. https://www.claritypharmaceuticals.com/news/ftd-67cu-sarbispsma/
2. 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing metastatic castrate resistant prostate cancer (SECuRE). ClinicalTrials.gov. Updated March 27, 2024. Accessed February 19, 2025. https://clinicaltrials.gov/study/NCT04868604