The phase 1 PROPELLER trial assessed the safety and efficacy of 64Cu-SAR-bisPSMA, and compared the imaging agent with 68Ga-PSMA-11 PET.
The PSMA-PET imaging product 64Cu-SAR-bisPSMA is safe and effective in patients with treatment-naïve, histologically confirmed prostate cancer who are scheduled for radical prostatectomy, according to data from the phase 1 PROPELLER trial presented at the 2023 Genitourinary Cancers Symposium.1,2
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.3
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).
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.”
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.
Looking forward, Clarity is preparing to launch a phase 3 study of 64Cu SAR-bisPSMA in patients with prostate cancer who have not yet received prostatectomy and/or other definitive treatment.
“It is very encouraging to see such positive imaging results from 64Cu SAR-bisPSMA, an agent we are very pleased to work with. The higher SUVmax was consistent across both independent, blinded, central readers, and, importantly, as shown on the images on the poster, 64Cu SAR-bisPSMA was able to detect disease outside of the primary lesion that was not detected with 68Ga PSMA-11. This is a very important result when it comes to patient management, and we are looking forward to further exploring these findings as we aim to better understand the benefits of 64Cu SAR-bisPSMA during the Phase III trial. With the high uptake of the product in tumors as well as the additional benefits of later imaging timepoints, we will continue to be involved in SAR-bisPSMA trials with the ultimate purpose of improving outcomes for our patients,” Louise Emmett, MD, MBChB, BSc, St Vincent's Hospital Sydney, principal investigator of the PROPELLER trial, stated in a press release.
1. 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.
2. PROPELLER Trial Results – SAR-bisPSMA Safe, Well Tolerated and Efficacious in the Detection of Prostate Cancer. Published online February 14, 2023. Accessed February 24, 2023. https://www.claritypharmaceuticals.com/news/propeller_results
3. 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