Clarity Pharmaceuticals has announced positive initial results from its Phase 1/2 COBRA trial, demonstrating that 64Cu-SAR-bisPSMA is safe and highly effective in detecting prostate cancer lesions in patients with biochemical recurrence (BCR) who had negative or equivocal standard-of-care (SOC) imaging.
The multi-center US-based trial enrolled 52 patients with BCR of prostate cancer following definitive therapy, with 42 included in the efficacy endpoint calculations. The median PSA at study entry was 0.9 ng/mL (range 0.25–17.60), notably lower than in registrational studies for currently approved PSMA PET agents.
Next-Day Imaging Reveals Significantly More Lesions
A standout finding from the COBRA trial was the significant advantage of next-day imaging, a capability unique to 64Cu-based diagnostics due to copper-64's optimal half-life and the SAR Technology's ability to prevent in-vivo leakage of copper isotopes.
The number of lesions identified by 64Cu-SAR-bisPSMA on next-day imaging (Day 1) almost doubled compared to same-day imaging (Day 0), increasing from 53-80 lesions to 82-153 lesions across readers. The detection of lesions in pelvic lymph nodes, a common site of prostate cancer metastases, more than doubled with a median increase of 108.3% on next-day imaging.
Dr. Neal Shore MD, FACS, Lead Principal Investigator in the COBRA trial and Medical Director of Carolina Urologic Research Centre, commented: "We are very enthusiastic regarding the data from the early phase COBRA trial as 64Cu-SAR-bisPSMA was confirmed to be safe and effective in detecting PC lesions in patients with BCR who came into the study with negative or equivocal scans using SOC imaging."
Clinical Impact on Patient Management
The trial demonstrated significant clinical impact, with investigators indicating they would change the treatment plan for approximately 50% of patients based on 64Cu-SAR-bisPSMA scan results. Among these patients, two-thirds (67%) proceeded to receive systemic and/or focal therapy.
In patients where SOC imaging was unable to detect any lesions, up to approximately 60% had lesions identified by same-day 64Cu-SAR-bisPSMA imaging, increasing to up to 80% on next-day imaging, with high specificity on both days.
Dr. Shore emphasized: "When detecting recurrence of PC, it is important to visualise small lesions, as reliable imaging of low volume tumor burden can affect treatment decision making. In the COBRA trial, we saw that 64Cu-SAR-bisPSMA positron emission tomography (PET) informed potential changes in the treatment plan in approximately half of the patients."
Study Design and Efficacy Endpoints
The COBRA trial employed rigorous methodology following regulatory guidance to achieve high standards in clinical research. The study design included blinded central readers for 64Cu-SAR-bisPSMA scans and a separate blinded expert panel to determine the reference standard, removing potential biases in assessment.
Primary efficacy endpoints included patient-level correct detection rate (CDR) and region-level positive predictive value (PPV). The CDR range across central readers on Day 0 was 21.4–28.6%, increasing to 28.6–38.1% on Day 1. The region-level PPV on Day 0 range was 39.1–44.8% and on Day 1 was 32.7–43.3%.
The specificity of prostate cancer detection in the pelvic lymph nodes was high across all readers and on both days (range 93.8–96.9% on Day 0 and 81.3–87.9% on Day 1).
Dr. Alan Taylor, Clarity's Executive Chairperson, noted that these results were impacted by the conservative study design: "The COBRA trial design was built to reflect the gold standard in clinical research and took a very conservative approach. Given we identified a large number of lesions with 64Cu-SAR-bisPSMA that were not visible with SOC scans, a number that was not anticipated when the protocol was prepared, it was not feasible nor ethical to verify all of these lesions with biopsy when caring for the patient."
Logistical Advantages for Clinical Implementation
Beyond clinical benefits, 64Cu-SAR-bisPSMA offers significant logistical and manufacturing advantages compared to currently used PSMA agents. The product can be shipped as ready-to-use from a central manufacturing facility on-demand, providing flexibility and reliability to patients and treating staff.
The longer shelf-life of 64Cu-based products, coupled with the advantages of the SAR Technology, could expand access to PSMA PET for prostate cancer patients in underserved and broad geographical areas, addressing limitations of approved PSMA agents due to their short half-life.
Advancing to Phase 3 Trials
Based on these promising results, Clarity has already commenced its registrational Phase 3 CLARIFY trial (NCT06056830) to assess the diagnostic performance of 64Cu-SAR-bisPSMA in detecting regional nodal metastasis in participants with high-risk prostate cancer prior to radical prostatectomy.
The CLARIFY study, which expects to recruit 383 participants across multiple clinical sites in the United States and Australia, will evaluate imaging at two timepoints: day of administration and approximately 24 hours post-administration. As a registrational trial, the final study results are intended to support an application to the US FDA for approval of 64Cu-SAR-bisPSMA as a new diagnostic imaging agent in prostate cancer.
Dr. Taylor emphasized: "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."
