Phase 3 trial of 64Cu-SAR-bisPSMA in BCR of prostate cancer set to launch in 2025

The phase 3 AMPLIFY trial of ⁶⁴Cu-SAR-bisPSMA PET/CT in patients with biochemically recurrent prostate cancer is set to launch following positive feedback from an end-of-phase meeting with the FDA, Clarity Pharmaceuticals announced in a news release.¹

AMPLIFY is supported by data from the phase 1/2 COBRA trial and the phase 1 PROPELLER trial.

According to the company, patient recruitment for the study is set to begin in early 2025.

"We look forward to commencing recruitment in our registrational AMPLIFY trial early next year and continuing to build on the exceptional data that we have seen in our trials with ⁶⁴Cu-SAR-bisPSMA to date,” said Clarity's executive chairperson, Alan Taylor, PhD, in the news release.¹ “We believe that better diagnostic tools will help clinicians determine the best course of treatment for their patients, and our team and collaborators look forward to bringing this next-generation PSMA diagnostic to prostate cancer patients around the world."

The non-randomized, single-arm, open-label, multicenter trial will evaluate the ability of ⁶⁴Cu-SAR-bisPSMA PET/CT to detect biochemical recurrence of prostate cancer. 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 will 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.”

Currently, ⁶⁴Cu-SAR-bisPSMA has a fast track designation for PET imaging of prostate-specific membrane antigen-positive prostate cancer lesions with suspected metastasis in patients who are candidates for initial definitive therapy. The FDA granted the designation in August 2024 based on findings from Clarity’s ongoing clinical program for the imaging agent. This program includes assessment of the agent in patients with biochemical recurrence in the COBRA and AMPLIFY trials, and in patients with prostate cancer prior to radical prostatectomy in the PROPELLER and CLARIFY trials.

Data on ⁶⁴Cu-SAR-bisPSMA

The initiation of the phase 3 AMPLIFY trial is supported by data from the phase 1/2 COBRA trial (NCT05249127) and the phase 1 PROPELLER trial (NCT04839367).

Data from the phase 1/2 COBRA trial demonstrated the safety and efficacy of the agent in detecting prostate cancer lesions in patients with biochemical recurrence.² Overall, data showed that ⁶⁴Cu-SAR-bisPSMA was able to identify lesions in approximately 60% of patients on same-day imaging and up to 80% on next-day imaging in whom standard of care imaging was unable to detect any lesions.

Further, the correct detection rate (defined as the proportion of true positive patients who had at least 1 evaluable reference standard data point among all participants) ranged from 21.4% to 28.6% among 3 central readers on day 0 and 28.6% to 38.1% on day 1. The region-level positive predictive value (defined at the proportion of true positive regions ⁶⁴Cu-SAR-bisPSMA PET/CT scan with corresponding evaluable reference standard among all positive regions) ranged from 39.1% to 44.8% on day 0 and 32.7% to 43.3% on day 1 across all readers.

According to Clarity, findings from this study informed planning for the phase 3 AMPLIFY trial.

⁶⁴Cu-SAR-bisPSMA was also assessed in the phase 1 PROPELLER trial, which demonstrated favorable safety and efficacy of the agent in patients with prostate cancer prior to radical prostatectomy.^3,4 In total, the study enrolled 30 patients with prostate cancer who were set to undergo radical prostatectomy and lymph node dissection.

Data showed that ⁶⁴Cu-SAR-bisPSMA was safe and well-tolerated among all patients in the study. The recommended dose was determined to be 200 MBq, as this cohort demonstrated the highest scores for imaging quality following review by 2 independent blinded central readers. In comparison with ⁶⁸Ga PSMA-11, ⁶⁴Cu-SAR-bisPSMA showed higher SUVmax values in patients who received the 200 MBq dose (n = 18).

Results from the PROPELLER trial led to the start of the ongoing registrational phase 3 CLARIFY trial (NCT06056830) in the same patient population.

In total, the phase 3 trial plans to enroll 383 patients across multiple clinical sites in the United States and Australia. The study will assess the diagnostic performance of ⁶⁴Cu-SAR-bisPSMA in detecting regional node metastasis prior to radical prostatectomy in patients who have high-risk prostate cancer. Participants will be evaluated at 2 time points: day 1 (day of administration) and day 2 (approximately 24 hours after administration).

Final completion of the CLARIFY trial is expected for early 2025.⁵

References

1. 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. Published online and accessed October 14, 2024. 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

2. Initial COBRA results: Clarity’s SAR-bisPSMA is safe and highly effective in detecting tumours in prostate cancer patients. Phase 3 planning underway. News release. Clarity Pharmaceuticals. February 15, 2024. Accessed October 14, 2024. https://www.claritypharmaceuticals.com/news/cobra_results/

3. Emmett L, Wong V, Lenzo N, Lengyelova E, Biggin C. Positron emission tomography of patients with confirmed prostate cancer using 64Cu-SAR-bisPSMA. J Clin Oncol. 41, 2023 (suppl 6; abstr 318). doi:10.1200/JCO.2023.41.6_suppl.318

4. PROPELLER trial results – SAR-bisPSMA safe, well tolerated and efficacious in the detection of prostate cancer. News release. Clarity Pharmaceuticals. February 14, 2023. Accessed October 14, 2024. https://www.claritypharmaceuticals.com/news/propeller_results/

5. Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy (CLARIFY). ClinicalTrials.gov. Last updated July 31, 2024. Accessed October 14, 2024. https://clinicaltrials.gov/study/NCT06056830