Phase 3 trial of 64Cu-SAR-bisPSMA in prostate cancer launches

The phase 3 CLARIFY trial (NCT06056830) exploring the diagnostic performance of ⁶⁴Cu-SAR-bisPSMA in patients with prostate cancer has commenced following the initiation of the first clinical trial site at the Urology Cancer Center/XCancer in Omaha, Nebraska, announced Clarity Pharmaceuticals, the developer of the theranostic, in a news release.¹

The CLARIFY trial expects primary completion results in early 2025.

The trial expects to enroll 383 patients across multiple clinical sites in the US and Australia, with the first patient in the trial expected to undergo imaging by the end of 2023.

The phase 3 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).

According to Clarity Pharmaceuticals, the final results are intended to support an application to the FDA for approval of ⁶⁴Cu-SAR-bisPSMA for imaging in patients with prostate cancer.

“We are excited to commence our first registrational Phase 3 trial with our optimized SAR-bisPSMA agent. The CLARIFY trial is based on compelling preclinical and clinical data, including our completed PROPELLER trial. It demonstrated the excellent safety profile and superior performance of ⁶⁴Cu-SAR-bisPSMA compared [with] 68Ga-PSMA-11 also in patients with prostate cancer prior to radical prostatectomy, guiding the study design for the CLARIFY trial,” said Alan Taylor, the executive chairperson for Clarity Pharmaceuticals, in the news release.¹

The phase 1 PROPELLER trial (NCT04839367) enrolled 30 patients with prostate cancer who were set to undergo radical prostatectomy and lymph node dissection. The primary end points included safety, tolerability, and efficacy of the agent, and the secondary end point was to determine the optimal dose level for subsequent trials. The study also compared the diagnostic properties of ⁶⁴Cu-SAR-bisPSMA with that of ⁶⁸Ga PSMA-11 as an exploratory objective.^2,3

Overall, data from the PROPELLER trial showed that ⁶⁴Cu-SAR-bisPSMA was safe and well-tolerated among all patients included 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). In reader 1 of this cohort, ⁶⁴Cu-SAR-bisPSMA was able to detect primary prostate cancer in 100% (18/18) of patients, compared with 77.8% (14/18) of patients with ⁶⁸Ga-PSMA-11 PET/CT. Reader 2 in this cohort reported that ⁶⁴Cu-SAR-bisPSMA was able to detect primary prostate cancer in 85.7% of patients (12/14; 4 scans were determined by the reader to be non-evaluable), and ⁶⁸Ga-PSMA-11 PET/CT was able to detect primary prostate cancer in 83.3% (15/18) of patients.

“The PROPELLER trial showed significantly higher uptake of ⁶⁴Cu-SAR-bisPSMA in PSMA-expressing lesions compared [with] an approved standard-of-care PSMA imaging agent, potentially enabling the diagnosis of additional and smaller lesions. CLARIFY will also investigate the benefits of delayed imaging in this patient group, a feature that has shown real benefits to patients so far and is not available with the first-generation PSMA imaging agents using gallium-68 or fluorine-18, which have very short half-lives and exhibit low sensitivity in detecting cancerous lesions,” Taylor explained in the news release.¹

The CLARIFY trial expects primary completion results in early 2025.

Taylor concluded, “The prostate cancer market is a key focus area for Clarity as there is a high unmet need for diagnostics and therapy, and we believe our theranostic SAR-bisPSMA product has the potential to improve diagnosis, therapy and ultimately change patients' lives. We look forward to progressing this trial to validate and expand upon the positive data we have accumulated so far with our SAR-bisPSMA product. With this trial, our aspiration is that with improved diagnostic tools, clinicians will be empowered to make more informed decisions regarding the best course of treatment for their patients."¹

References

1. Registrational phase III CLARIFY trial in prostate cancer commences. News release. Clarity Pharmaceuticals. November 30, 2023. Accessed December 5, 2023. https://www.prnewswire.com/news-releases/registrational-phase-iii-clarify-trial-in-prostate-cancer-commences-302001515.html

2. 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

3. PROPELLER trial results – SAR-bisPSMA safe, well tolerated and efficacious in the detection of prostate cancer. News release. Clarity Pharmaceuticals. February 14, 2023. Accessed December 5, 2023. https://www.claritypharmaceuticals.com/news/propeller_results/