FDA Grants Breakthrough Therapy Designation to 64Cu-SAR-bisPSMA for PSMA PET in Biochemically Recurrent Prostate Cancer

The FDA has granted breakthrough therapy designation to ⁶⁴Cu-SAR-bisPSMA for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)–positive lesions in patients with prostate cancer with suspected biochemical recurrence (BCR) based on an elevated serum prostate-specific antigen (PSA) level.¹

According to Clarity Pharmaceuticals, the developer of the agent, this is the first breakthrough therapy designation granted in PSMA PET imaging.¹

The designation was supported in part by findings from the phase 2 Co-PSMA trial (NCT06907641), data from which were published in European Urology. The study compared next-day ⁶⁴Cu-SAR-bisPSMA PET/computed tomography (CT) with standard-of-care gallium Ga 68 PSMA-11 (⁶⁸Ga-PSMA-11) PET/CT in 50 patients with BCR following radical prostatectomy.^1,2 Data for the study’s primary end point showed the mean number of lesions per patient was 1.26 with ⁶⁴Cu-SAR-bisPSMA at 24 hours vs 0.48 with ⁶⁸Ga-PSMA-11, translating to a difference of 0.78 (95% CI, 0.52-1.04) and a ratio of 2.63 (95% CI, 1.64-4.20; P < .0001).²

At the patient level, 78% of patients had positive findings on next-day ⁶⁴Cu-SAR-bisPSMA imaging compared with 36% for ⁶⁸Ga-PSMA-11. Against a composite reference standard, the true-positive rate was 71% with ⁶⁴Cu-SAR-bisPSMA vs 29% with ⁶⁸Ga-PSMA-11 (n = 34). The false-negative rate was 21% vs 65%, respectively. Planned management changed between scans in 44% of the 50-patient cohort.

"Receiving this breakthrough therapy designation is one of the most significant milestones in our prostate cancer program to date," said Alan Taylor, PhD, executive chairperson of Clarity Pharmaceuticals.^{1 “}The FDA's award of the first breakthrough therapy designation in the history of PSMA PET imaging highlights both the unmet need for more accurate detection of recurrent prostate cancer lesions and the significance of the data generated.”

What is the mechanism of action of ⁶⁴Cu-SAR-bisPSMA?

⁶⁴Cu-SAR-bisPSMA is a bivalent PSMA-targeting radiopharmaceutical in which 2 PSMA-binding agents are linked to a sarcophagine (SAR) chelator. The SAR chelator holds copper in a cage-like structure designed to prevent copper from leaking into the body. Copper-64 has a half-life of 12.7 hours, which allows imaging up to approximately 30 hours after injection and supports both same-day and next-day scans.¹The same molecule can carry copper-67 for therapeutic use, an approach the company is developing as a theranostic platform.

How was the Co-PSMA trial designed?

Co-PSMA was a prospective, investigator-initiated, head-to-head imaging trial conducted at St Vincent's Hospital in Sydney, Australia, with support from Clarity.^1,2 Eligible patients had BCR after radical prostatectomy, a PSA level of 0.2 to 0.75 ng/mL, and no prior salvage therapy; the median PSA level among enrolled patients was 0.43 ng/mL (interquartile range, 0.31-0.63).²

Each patient underwent ⁶⁸Ga-PSMA-11 PET/CT according to institutional protocol, as well as ⁶⁴Cu-SAR-bisPSMA PET/CT at 1 hour (same day) and 24 hours (next day) after injection, with all scans acquired within 3 weeks on the same digital PET camera.^1,2 Images were prospectively reported and triple read for concordance, and planned management was recorded after each imaging study.² The reference standard incorporated biopsy, response to targeted treatment without androgen deprivation therapy, PSA changes during observation, and repeat imaging.

The primary end point was the mean per-patient difference in the number of lesions detected between the 2 agents, assessed with paired t tests and mixed-effects Poisson regression.

What are the next steps for ⁶⁴Cu-SAR-bisPSMA?

The agent previously received FDA fast track designation in August 2024 for PET imaging of PSMA-positive prostate cancer lesions in patients with suspected metastasis who are candidates for initial definitive therapy.⁴

Additionally, ⁶⁴Cu-SAR-bisPSMA is being evaluated in 2 registrational phase 3 trials, with topline data from both expected in the first half of 2027.¹

The phase 3 AMPLIFY trial (NCT06970847) is a nonrandomized, single-arm, open-label, multicenter diagnostic study enrolling patients with rising or detectable PSA levels (>0.2 ng/mL) after initial definitive treatment at sites in the United States and Australia. Co-primary end points are patient-level correct detection rate and region-level positive predictive value, each assessed separately for same-day (1-4 hours) and next-day (approximately 24 hours) imaging. AMPLIFY reached its enrollment target of approximately 220 patients in March 2026.

The phase 3 CLARIFY trial (NCT06056830) is a nonrandomized, open-label, single-arm, blinded-review diagnostic study in patients with untreated, histopathology-confirmed high-risk prostate cancer proceeding to radical prostatectomy with pelvic lymph node dissection.^1,3 Its co-primary end points are the sensitivity and specificity of day 1 and day 2 ⁶⁴Cu-SAR-bisPSMA PET for detecting pelvic nodal metastases compared with a standard of truth.³ CLARIFY reached its enrollment target in October 2026.¹

References

1. First FDA Breakthrough Therapy designation in PSMA PET imaging granted to Cu-64 SAR-bisPSMA in biochemical recurrence of prostate cancer. News release. Clarity Pharmaceuticals. November 12, 2026. Accessed November 12, 2026. https://www.prnewswire.com/news-releases/first-fda-breakthrough-therapy-designation-in-psma-pet-imaging-granted-to-cu-64-sar-bispsma-in-biochemical-recurrence-of-prostate-cancer-302937430.html
2. Khan S, Papa N, Kneebone A, et al. Prospective comparison of ⁶⁴Copper [⁶⁴Cu]SAR-bisPSMA vs ⁶⁸Gallium [⁶⁸Ga] PSMA-11 PET/CT for biochemical recurrence of prostate cancer following radical prostatectomy (Co-PSMA trial). Eur Urol. 2026;89(6):512-520. doi:10.1016/j.eururo.2026.03.001
3. Positron emission tomography using ⁶⁴Cu-SAR-bisPSMA in participants with high-risk prostate cancer prior to radical prostatectomy. ClinicalTrials.gov. Updated September 11, 2026. Accessed November 12, 2026. https://clinicaltrials.gov/study/NCT06056830
4. Clarity receives FDA fast track designation for ⁶⁴Cu-SAR-bisPSMA. News release. Clarity Pharmaceuticals. August 22, 2024. Accessed August 26, 2024. https://www.claritypharmaceuticals.com/news/fast-track/