64Cu-SAR-bisPSMA can detect small prostate cancer lesions, new data show

Additional data from the phase 1/2 COBRA study (NCT05249127) highlight the ability of 64Cu-SAR-bisPSMA to detect prostate cancer lesions less than 5 mm in size, which are challenging to detect using current standard of care (SOC) imaging, according to a news release from Clarity Pharmaceuticals, the developer of the diagnostic.¹

Findings from the phase 1/2 COBRA study will be used to inform a registrational phase 3 trial of the agent in patients with BCR of prostate cancer.

“The cornerstone of better therapy is better diagnosis, and we are incredibly excited about the substantial degree of improvement in detection of lesions with our bisPSMA product compared [with] SOC imaging,” said Alan Taylor, PhD, executive chairperson for Clarity, in the news release.¹ “This difference is similar to comparing the old Hubble telescope to the new James Webb telescope, allowing us to visualize with much greater clarity, and to effectively change the paradigm of treatment to considerably improve the outcomes for patients with [prostate cancer]. Innovative products like 64Cu-SAR-bisPSMA may prevent many millions of men from receiving inappropriate treatments and suffering substantial debilitating [adverse] effects from surgery or other therapies.”

Overall, data showed that lesions less than 5 mm in size were detected across readers in 14% (7 of 50) of patients. Lesions were identified in the bone, pelvic, and extra-pelvic lymph node regions. The smallest lesion identified in the study was 2.6 x 1.9 mm, which was detected in the pelvic lymph node region.

Additionally, mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax), assessed in up to 25 lesions per patient on same-day and next-day imaging, increased by an average of 82% and 87% across all readers, respectively. Tumor-to-background ratio (TBR), assessed in the same fashion, demonstrated an average 4.8-fold increase across all readers. Lesions less than 5 mm in size showed an average SUVmean, SUVmax, and TBR value of 16.3, 16.8, and 90.1, respectively, across all readers. 

Taylor added in the news release,¹ “When combining the optimized dual PSMA targeting agent with the ideal half-life of copper-64 (64Cu), we continue to observe higher uptake and retention of 64Cu-SAR-bisPSMA in [prostate cancer] lesions. We believe the ability of 64Cu-SAR-bisPSMA to detect such small lesions is due to the higher uptake and retention of the product over time with high contrast (parameters measured by SUVmean, SUVmax, and TBR). Small lesions become more readily detectable if the uptake of the product in the lesion is high and the background noise on the image is low. This effect enhances the contrast, making the lesion easier to detect, providing clinicians with valuable information on how to best treat their patients.”

Overall, the multicenter, single-arm, non-randomized phase 1/2 COBRA trial enrolled and imaged patients with biochemically recurrent prostate cancer who had negative or equivocal scans on SOC imaging. All patients underwent PET/CT scans on day 0 and day 1 (1-4h and 24±6h post-dose, respectively). All scans were interpreted by 3 blinded central readers.

Additional data from COBRA

Initial data from the phase 1/2 COBRA trial were published earlier this year, supporting the safety and efficacy of 64Cu-SAR-bisPSMA in detecting prostate cancer lesions in patients with biochemical recurrence (BCR) of prostate cancer following definitive therapy.²

Overall, 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.

Further, the specificity of prostate cancer detection in pelvic lymph nodes ranged from 93.8% to 96.9% on day 0 and 81.3% to 87.9% on day 1. The patient-level detection rate (defined as the proportion of patients with a positive 64Cu-SAR-bisPSMA PET/CT scan among all participants) ranged from 44% to 58% on day 0 and increased to 58% to 80% on day 1.

Among patients in whom SOC imaging was unable to detect any lesions, 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.

According to the investigators, data from the trial confirm the benefits of delayed imaging in this patient population. Altogether, 64Cu-SAR-bisPSMA led to an approximately 91% median increase in the detection of lesions on next-day imaging compared with same-day imaging. Further, the number of lesions detected in the pelvic lymph node region more than doubled on next-day imaging compared with same-day imaging, increasing from 53 to 80 total lesions on day 0 to 82 to 153 lesions on day 1 (median increase, 108.3% across all readers).

Based on findings from 64Cu-SAR-bisPSMA imaging, the investigators indicated that they would change the treatment plan in 48% of patients. Of these, 67% of patients went on to receive systemic and/or focal therapy.

According to Clarity, findings from the phase 1/2 COBRA study will be used to inform a registrational phase 3 trial of the agent in patients with BCR of prostate cancer.

References

1. Additional COBRA results: SAR-bisPSMA detects lesions in the 2-millimetre range. News release. Clarity Pharmaceuticals. March 6, 2024. Accessed March 7, 2024. https://www.claritypharmaceuticals.com/news/cobra_additional_results/

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 March 7, 2024. https://www.claritypharmaceuticals.com/news/cobra_results/