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

The phase 3 CLARIFY trial (NCT06056830) is launching to explore the PSMA-PET imaging product ⁶⁴Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy, according to Clarity Pharmaceuticals and PSI CRO AG, the companies collaborating on the trial.¹

Previously reported data from the phase 1 PROPELLER trial showed that ⁶⁴Cu-SAR-bisPSMA is safe and effective in patients with treatment-naïve, histologically confirmed prostate cancer who are scheduled for radical prostatectomy.

The open-label, single-arm trial is aiming to recruit 383 patients with previously untreated, histologically confirmed, high-risk adenocarcinoma of the prostate who are scheduled to receive radical prostatectomy with pelvic lymph node dissection. The trial is using NCCN criteria to define high-risk as clinical stage ≥T3a, Grade Group ≥4, or PSA >20 ng/mL.²

The primary end point of the trial is the diagnostic capability of ⁶⁴Cu-SAR-bisPSMA PET to identify regional node metastases. Imaging timepoints for patient evaluation will be on the day of ⁶⁴Cu-SAR-bisPSMA PET administration (day 1) and about 24 hours following administration (day 2). Among the key secondary end points are safety/tolerability and the consistency of the interpretations of ⁶⁴Cu-SAR-bisPSMA PET/CT from 3 central readers.²

"We are very excited to move one step closer to initiating our first registrational Phase III trial. With recent positive and valuable guidance from the US FDA in relation to our ⁶⁴Cu-SAR-bisPSMA program, we look forward to commencing recruitment into the CLARIFY trial shortly and to gathering more data on this next-generation product to confirm the compelling preclinical and clinical trial results to date,” Dr Alan Taylor, executive chairman of Clarity, commented in a news release.

"The positive results from our completed PROPELLER trial showed that ⁶⁴Cu-SAR-bisPSMA is safe and its uptake in PSMA-expressing cancer lesions was significantly higher compared to an approved standard-of-care PSMA imaging agent for prostate cancer in Australia and the US. This may enable diagnosis of additional and smaller lesions, which we observed in our PROPELLER trial, and we are eager to investigate the further benefits of delayed imaging, particularly in this patient population, a characteristic not available to the first generation of PSMA diagnostic agents. Furthermore, we believe that the additional shelf-life of up to 48 hours will not only allow clinics greater flexibility in scheduling of the scans, but also improve patients' access to care in clinics and geographic areas where the short half-life of current PSMA PET tracers restricts the use of radiopharmaceuticals,” added Taylor.

Prior results with ⁶⁴Cu-SAR-bisPSMA

Previously reported data from the phase 1 PROPELLER trial showed that ⁶⁴Cu-SAR-bisPSMA is safe and effective in patients with treatment-naïve, histologically confirmed prostate cancer who are scheduled for radical prostatectomy.³

Overall, the multi-center, blinded review, phase 1 PROPELLER trial assessed the safety, tolerability, and efficacy of ⁶⁴Cu-SAR-bisPSMA. The study also compared ⁶⁴Cu-SAR-bisPSMA to ⁶⁸Ga-PSMA-11 PET, a standard radiotracer used for the imaging of PSMA-positive lesions in patients with prostate cancer.

The study prospectively enrolled 30 patients. To enroll in the trial, patients must have had at least 1 of these intermediate- to high-risk features: a PSA level ≥10.0 ng/ml within 12 weeks prior to enrolling, a Gleason score of 7 (4+3) or higher, and/or a clinical stage ≥T2b.⁴

The median patient age was 64 years (range, 50-75). The TNM stages were unknown (n = 2), T1a (n = 1), T1c (n = 3), T2a (n = 7), T2b (n = 5), T2c (n = 9), T3a (n = 3), T3b (n = 1), N0 (n = 28).³

The International Society of Urologic Pathologists (ISUP) grades were 2 (n = 3), 3 (n = 12), 4 (n = 7), and 5 (n = 8). The mean PSA level was 10.49 ng/mL (SD, 8.08).

Patients were administered a 68Ga-PSMA-11 PET/CT at screening about 45 to 60 minutes following injection. In a 1:1:3 ratio, patients received 100 MBq (n = 6), 150 MBq (n = 6), or 200 MBq (n = 18) of ⁶⁴Cu-SAR-bisPSMA followed by a PET/CT at 2 to 4 hours after injection.

The safety and efficacy of the ⁶⁴Cu-SAR-bisPSMA and 68Ga-PSMA-11 PET/CT scans were determined by 2 independent, blinded, central readers. After these assessments, patients subsequently received their scheduled prostatectomy with pelvic lymph node dissection.

The highest scores for image quality for both readers were for the 18-patient 200 MBq of ⁶⁴Cu-SAR-bisPSMA cohort. In this cohort, for reader 1, ⁶⁴Cu-SAR-bisPSMA was able to detect primary prostate cancer in 100% (18/18) of patients and ⁶⁸Ga-PSMA-11 PET/CT was able to detect primary prostate cancer for 77.8% (14/18) of patients.

Reader 2 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.

All scans not determined to be positive were categorized as indeterminate; there were no scans deemed to be negative.

According to the authors, “The resulting true positive rate and false negative rate were similar for ⁶⁴Cu-SAR-bisPSMA and 68Ga-PSMA-11 PET/CT.”³

The researchers assessed uptake of the imaging agents using maximum Standardized Uptake Values (SUVmax) on the PET scan. These measurements showed higher update with ⁶⁴Cu SAR-bisPSMA versus ⁶⁸Ga PSMA-11, which led to brighter lesions.

Also of note, scans from a patient showed uptake of ⁶⁴Cu SAR-bisPSMA in a left pelvic lymph node, outside the prostate. This secondary disease was verified by histopathology. The readers did not detect the lesion on the ⁶⁸Ga PSMA-11 scan.

Regarding safety, ⁶⁴Cu SAR-bisPSMA was well tolerated. There was only 1 adverse event considered to be related to ⁶⁴Cu SAR-bisPSMA, which was grade 1 dysgeusia in 1 patient who received the 200 MBq dose.

References

1. Clarity and PSI kick off SAR-bisPSMA Phase III. Published online October 26, 2023. https://www.prnewswire.com/news-releases/clarity-and-psi-kick-off-sar-bispsma-phase-iii-301968210.html

2. NIH ClinicalTrials.gov. Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy (CLARIFY). Last updated October 13, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT06056830

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. NIH ClinicalTrials.gov. Positron Emission Tomography (PET) Imaging of Participants With Confirmed Prostate Cancer Using 64Cu-SAR-bisPSMA (PROPELLER) (PROPELLER) Last update August 18, 2021. Accessed December 9, 2021. https://clinicaltrials.gov/ct2/show/NCT04839367