64Cu-SAR-bisPSMA shows safety, efficacy in biochemically recurrent prostate cancer

Initial data from the phase 1/2 COBRA study (NCT05249127) support 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, according to a news release from Clarity Pharmaceuticals, the developer of the diagnostic.¹

According to Clarity, the current findings from the study will be used to inform a registrational phase 3 trial of the diagnostic in patients with BCR of prostate cancer.

“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 [prostate cancer] lesions in patients with BCR who came into the study with negative or equivocal scans using [standard of care] imaging. The trial demonstrates a clinical advantage of same-day and next-day imaging in detecting additional lesions as well as for potentially detecting low prostate-specific membrane antigen (PSMA) expressing or smaller lesions,” said principal investigator Neal Shore, MD, FACS, in the news release.¹ Shore is the medical director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina.

Overall, the correct detection rate (CDR, 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 (PPV, defined at the proportion of true positive regions 64Cu-SAR-bisPSMA PET/CT scan with corresponding evaluable reference standard among all positive regions) was 39.1% to 44.8% on day 0 and 32.7% to 43.3% on day 1.

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 (DR, 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 standard of care 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).

Regarding safety, there was 1 reported adverse event related to treatment with 64Cu-SAR-bisPSMA, which was a grade 2 worsening of type 2 diabetes and was resolved.

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.

“When detecting recurrence of [prostate cancer], it is important to visualize 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 PET informed potential changes in the treatment plan in approximately half of the patients. This makes a difference for patients who may then have insight into the location of their disease recurrence and thereby proceed to treatment of their cancer,” Shore said in the news release.¹

In total, the single-arm, non-randomized COBRA trial enrolled and imaged 52 patients who had negative or equivocal scans on standard-of-care imaging. Of those, 42 were included in the efficacy analysis. The median prostate-specific antigen (PSA) level among patients at study entry was 0.9 ng/mL (range, 0.25-17.6 ng/mL), which is low compared with the levels seen in the registrational studies for approved PSMA PET agents in BCR, according to the news release.

All patients in the current study underwent PET/CT scans on day 0 and day 1 (1-4h and 24±6h post-dose, respectively). The scans were compared with a composite reference standard consisting of histopathology, follow-up standard-of-care imaging, and/or PSA response to focal therapy. All scans were interpreted by 3 blinded central readers.

The primary efficacy end points for the study were the patient-level CDR and the region-level PPV.² The primary objectives of the study were to assess the safety and tolerability of 64Cu-SAR-bisPSMA as well as the agent’s ability to correctly detect recurrence of prostate cancer.

According to Clarity, the current findings from the study will be used to inform a registrational phase 3 trial of the diagnostic in patients with BCR of prostate cancer.

Shore concluded in the news release, “We look forward to additional data readouts from the trial and presenting the results at future international medical conferences. If the data from the COBRA trial can be substantiated in a registrational Phase 3 study, and if approved by the US FDA, this PET PSMA modality will impact care for patients with [prostate cancer].”¹

References

1. 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. Published online and accessed February 15, 2024. https://www.claritypharmaceuticals.com/news/cobra_results/

2. 64Cu-SAR-bisPSMA for Identification of Participants With Recurrence of Prostate Cancer (COBRA) (COBRA). ClinicalTrials.gov. Last updated August 31, 2023. Accessed February 15, 2024. https://clinicaltrials.gov/study/NCT05249127