Pivotal trial launches of 64Cu-SAR-bisPSMA in BCR of prostate cancer

The first clinical trial site has been activated in the pivotal phase 3 AMPLIFY trial (NCT06970847), evaluating the efficacy and safety of ⁶⁴Cu-SAR-bisPSMA in patients with biochemical recurrence (BCR) of prostate cancer, Clarity Pharmaceuticals announced in a news release.¹

Completion of the AMPLIFY trial is expected in December 2026.

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 BCR 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 pivotalphase 3 CLARIFY trial (NCT06056830) is assessing the agent in this indication.

"We are very excited to commence our second registrational phase III trial with the optimized SAR-bisPSMA agent in patients that are experiencing the return of their disease following treatment of the primary cancer,” said Clarity's Executive Chairperson, Alan Taylor, PhD, in the news release.¹ "The recent devastating news that former US President, Joe Biden, has been diagnosed with aggressive prostate cancer that has metastasized to the bone is yet another reminder that no man is safe from this insidious disease, and he joins over 3.3 million men in the US who live with prostate cancer today. Australia is also not immune. A recent public announcement revealed that MP Barnaby Joyce has recently been diagnosed with prostate cancer, and he joins over 250,000 Australian men who are living with prostate cancer today. These large numbers highlight the need for more timely and accurate diagnosis to safely and effectively treat the cancer with suitable therapies.”

About the AMPLIFY trial

Overall, the nonrandomized, single-arm, open-label, multicenter AMPLIFY trial will evaluate the ability of ⁶⁴Cu-SAR-bisPSMA PET/CT to detect prostate cancer lesions among patients with a rising or detectable prostate-specific antigen (PSA) level following initial definitive treatment.

The study plans to enroll approximately 220 patients across clinical trial sites in the US and Australia.³ To be eligible for enrollment, patients need to have a life expectancy of at least 6 months, a rising or detectable PSA level following definitive therapy, and an ECOG performance status of 0 to 2.

Those enrolled in the study will receive a single dose of ⁶⁴Cu-SAR-bisPSMA at the dose level of 200 MBq.

The primary end point is the patient-level correct detection rate and the region-level positive predictive value. 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).

Secondary end points include safety and tolerability, inter- and intra-reader variability, and detection rates in patients with negative or equivocal conventional imaging at baseline.

Clarity 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 US Food and Drug Administration (FDA) for approval of ⁶⁴Cu-SAR-bisPSMA as a new diagnostic imaging agent in biochemical recurrence (BCR) of prostate cancer.”

Completion of the trial is expected in December 2026.

Previous data on ⁶⁴Cu-SAR-bisPSMA

The phase 3 AMPLIFY trial was informed by data from the phase 1/2 COBRA trial (NCT05249127), which demonstrated the safety and efficacy of the agent in detecting prostate cancer lesions in patients with BCR who had negative or equivocal standard of care scans at study entry.

The investigators found that 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 (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.

Overall, the agent identified 53 to 80 lesions on day 0 vs 82 to 153 on day 1. The mean number of lesions 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.

REFERENCES

1. Registrational phase III AMPLIFY trial in biochemical recurrence of prostate cancer commences. News release. Clarity Pharmaceuticals. Published online and accessed May 20, 2025. https://www.prnewswire.com/news-releases/registrational-phase-iii-amplify-trial-in-biochemical-recurrence-of-prostate-cancer-commences-302459721.html

2. Clarity receives U.S. FDA fast track designation for Cu-64 SAR-bisPSMA in biochemical recurrence of prostate cancer. News release. Clarity Pharmaceuticals. January 24, 2025. Accessed May 20, 2025. https://www.claritypharmaceuticals.com/news/ftd-2/

3. The aim for this study is to investigate the ability of 64Cu-SAR-bisPSMA PET/​CT to detect recurrence of prostate cancer (AMPLIFY). ClinicalTrials.gov. Last updated May 14, 2025. Accessed May 20, 2025. https://clinicaltrials.gov/study/NCT06970847

4. 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