SABRE: Assessment of safety and efficacy of ⁶⁴Cu-SAR-BBN in patients with PSMA-negative biochemical recurrent prostate cancer.

TPS346 Background: Between 20-40% of patients with prostate cancer (PC) will relapse within 10 years of their primary PC treatment, as identified through rising prostate-specific antigen (PSA) levels. Early diagnosis of biochemical recurrence (BCR) with accurate staging is essential to informing optimal treatment decision-making. Approximately 20% of biochemically recurrent PC patients show low or no PSMA expression on prostate-specific membrane antigen (PSMA)-targeted PET. Consequently, these patients are unlikely to benefit from PSMA-targeted agents and represent a significant unmet need for both imaging and therapy. The Gastrin Releasing Peptide receptor (GRPr) is a transmembrane G-protein coupled receptor that is upregulated in many human cancers, including PC. 64 Cu-SAR-BBN, a GRPr-targeting agent, uses a radioactive form of copper, copper-64 ( 64 Cu), to image cancers using PET. Initial clinical data have shown that 64 Cu-SAR-BBN was able to detect lesions in 32% (8/25) of patients with BCR of PC and negative/equivocal PSMA PET. Methods: SABRE is a phase II, single arm, non-randomized, open-label study of 64 Cu-SAR-BBN administered to patients with BCR of PC following definitive therapy. Key eligibility criteria include confirmed adenocarcinoma of the prostate, recurrence of PC based on rising PSA after definitive therapy and negative or equivocal findings for PC on an approved PSMA PET. Approximately 50 patients will be enrolled. The objectives are to assess the safety of 64 Cu-SAR-BBN (200 MBq), and its ability to detect recurrent PC when traditional PSMA PET is not informative. Patients will complete a PET/CT on the same day (1 to 4 hours) and the next day (24 ±6 hours) post-dose. We hypothesize that delayed imaging may allow the detection of additional lesions compared to the scan performed on the same day of the administration of the product. The safety endpoint includes the incidence and severity of treatment-emergent adverse events and serious adverse events following the administration of 64 Cu-SAR-BBN. Efficacy endpoints include correct detection rate (participant level) and positive predictive value (at participant and region level) at each scan timepoint independently. The 64 Cu-SAR-BBN PET/CT scans will be assessed centrally by 3 independent, blinded readers. Each reader will evaluate the scans for the presence of pathological 64 Cu-SAR-BBN uptake in the prostate bed/gland, pelvic lymph nodes (LN), extra pelvic LN, visceral/soft tissue and bone regions. Patients will be followed for up to 180 days to verify the findings. The 64 Cu-SAR-BBN PET/CT results will then be assessed against a composite Reference Standard (histopathology, conventional imaging, and/or PSA levels) determined by an independent, blinded, central expert panel. 50% recruitment was reached on July 24, 2023. Clinical trial information: NCT05407311 .