64Cu-SAR-bisPSMA shows efficacy in detection of biochemically recurrent prostate cancer

The investigational PET imaging agent ⁶⁴Cu-SAR-bisPSMA was effective in detecting prostate cancer lesions in patients with biochemical recurrence and negative or equivocal standard of care (SOC) imaging, according to findings from the phase 1/2 COBRA trial (NCT05249127).¹

64Cu-SAR-bisPSMA is currently being assessed in the phase 3 AMPLIFY trial.

The data were presented at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.

In total, the COBRA study enrolled 52 patients, of whom 50 had evaluable PET imaging results. ⁶⁴Cu-SAR-bisPSMA was delivered at 200 MBq, and PET/CT imaging was performed on day 0 (1-4 hours post-dose) and day 1 (24±6 hours post-dose). Scans were compared against a reference standard.

Overall, ⁶⁴Cu-SAR-bisPSMA detected lesions in up to 80% of patients. According to the authors, “Histopathology confirmed the presence of [prostate cancer] in lesions identified by ⁶⁴Cu-SAR-bisPSMA in up to 78% of cases in which biopsies were performed.”

The detection rate across all 3 readers ranged from 44% to 58% (95% CI, 30%-71.8%) on day 0 and increased to 58% to 80% (95% CI, 43.2%-90%) on day 1.

The correct detection rate (CDR; proportion of true positive patients out of all patients who had at least 1 reference standard datapoint) also increased on next-day imaging, ranging from 19% to 26.2% (95% CI, 8.6%-42.0%) on day 0 and 26.2% to 33.3% (95% CI, 13.9%-49.5%) on day 1. When assessing the CDR against the gold standard of histopathology as the reference standard, the CDR was notably higher, ranging from 44.4% to 55.6% on day 0 and 55.6% to 77.8% on day 1 (n = 9).

According to the authors, “This highlights the limitations of using less sensitive methods (e.g. current SOC imaging) to verify the ⁶⁴Cu-SAR-bisPSMA PET findings.”

Overall, the agent identified 53 to 80 lesions on day 0 vs 82 to 153 on day 1. The mean number of lesion per patient with a positive 64Cu-SAR-bisPSMA scan ranged from 2.4 to 2.8 on day 0 and 2.8 to 4.1 on day 1.

The investigators also found that ⁶⁴Cu-SAR-bisPSMA imaging led to a change in treatment plans in 48% (24 of 50) of patients.

Further assessment of ⁶⁴Cu-SAR-bisPSMA

⁶⁴Cu-SAR-bisPSMA was granted a fast track designation from the FDA in January 2025 for PET imaging of prostate-specific membrane antigen (PSMA)-positive lesions in patients with biochemical recurrence of prostate cancer following initial definitive therapy.² The agent also has a fast track designation in patients with suspected metastasis of prostate cancer who are candidates for initial definitive therapy.

The agent is being further assessed in the ongoing phase 3 AMPLIFY trial.

The company announced plans to launch the AMPLIFY trial in October 2024.³ Overall, the non-randomized, single-arm, open-label, multicenter trial will further evaluate the ability of ⁶⁴Cu-SAR-bisPSMA PET/CT to detect prostate cancer lesions among patients with biochemical recurrence. Efficacy will be assessed on both same-day imaging (day 1, day of administration) and next-day imaging (day 2, approximately 24 hours post-administration).

The study plans to enroll approximately 220 patients who have rising or detectable prostate-specific antigen (PSA) levels following initial definitive treatment for prostate cancer.

Clarity Pharmaceuticals noted in the news release, “As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of ⁶⁴Cu-SAR-bisPSMA as a new diagnostic imaging agent in prostate cancer in patients with BCR.”²

REFERENCES

1. Nordquist L, Lengyelova E, Saltzstein D, et al. COBRA: Assessment of the efficacy of 64Cu-SAR-bisPSMA using histopathology as reference standard in patients with biochemical recurrence of prostate cancer following definitive therapy. J Clin Oncol. 2025;43 (suppl 5). Abstract 44. doi:10.1200/JCO.2025.43.5_suppl.44

2. Clarity receives U.S. FDA Fast Track Designation for Cu-64 SAR-bisPSMA in biochemical recurrence of prostate cancer. News release. January 24, 2025. Accessed March 6, 2025. https://www.claritypharmaceuticals.com/news/ftd-2/

3. Positive guidance from the U.S. FDA on 64Cu-SAR-bisPSMA phase III trial in patients with recurrence of prostate cancer. News release. Clarity Pharmaceuticals. October 14, 2024. Accessed March 6, 2025. https://www.prnewswire.com/news-releases/positive-guidance-from-the-us-fda-on-64cu-sar-bispsma-phase-iii-trial-in-patients-with-recurrence-of-prostate-cancer-302274687.html