Abstract
TPS5129 Background: Prostate cancer (PC) is the second most prevalent cancer in men globally. Metastasis typically involves pelvic lymph nodes (LNs), progressing to extra-pelvic LNs as well as bone, liver and lungs. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is expressed in normal, benign and malignant prostate tissue. PSMA is strongly overexpressed in PC, making it an ideal target for imaging and therapy. 64 Cu-SAR-bisPSMA offers several potential advantages over approved positron emission tomography (PET) imaging agents targeting prostate-specific membrane antigen (PSMA), including its bivalent structure (bisPSMA) and longer half-life of 64 Cu (12.7h vs. < 2h for 18 F and 68 Ga). This has been shown to lead to prolonged tumor retention, 2-3 times higher tumor uptake and detection of additional PC lesions using 64 Cu-SAR-bisPSMA compared to approved PSMA PET agents. In this phase 3 diagnostic trial, we aim to establish the diagnostic performance of this radiotracer in men with high-risk prostate cancer. Methods: CLARIFY (NCT06056830) is a multi-center, single-arm, non-randomized, open-label Phase 3 diagnostic study of 64 Cu-SAR-bisPSMA. The target population is patients with untreated, histopathology-confirmed PC with high-risk features, who are proceeding to radical prostatectomy (RP) with pelvic lymph node dissection (PLND). The primary objective is to assess the sensitivity and specificity of 64 Cu-SAR-bisPSMA PET to detect regional (pelvic) nodal metastases. Secondary objectives include assessment of safety and determining the positive and negative predictive value of 64 Cu-SAR-bisPSMA PET for the detection of PC within the pelvic LN field. A total of 383 patients will be enrolled. Standard of care (SOC) imaging will be captured at screening (e.g. computed tomography [CT], approved PSMA PET/CT). Eligible patients will receive a single administration of 64 Cu-SAR-bisPSMA (200 MBq) followed by a PET/CT scan on Day 1 (1-4 hours post-dose) and on Day 2 (24±6 hours post-dose). Patients will proceed to RP with PLND. The specimens from surgery will be processed and analyzed locally to derive the Standard of Truth (SOT). The 64 Cu-SAR-bisPSMA PET/CT scans will be interpreted locally and by 3 independent, blinded, central readers. Each reader will assess the scans for 64 Cu-SAR-bisPSMA uptake in the pelvic LNs, prostate gland, extra-pelvic LNs, visceral/soft tissue and bone. The diagnostic performance of 64 Cu-SAR-bisPSMA will be based on the scan result for the respective day independently (Day 1 and 2) matched against the SOT. The diagnostic performance of 64 Cu-SAR-bisPSMA PET to detect PC within the pelvic LNs will be compared to that of the baseline SOC imaging using histopathology results. The study is open for recruitment in sites in the United States, with additional sites in start-up in Australia. Clinical trial information: NCT06056830 .