CLARIFY: Positron emission tomography using ⁶⁴ Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy—A phase 3 diagnostic performance study.

Abstract

TPS429 Background: Prostate cancer (PC) is the second most prevalent cancer in men globally. In men with newly diagnosed, high-risk disease, PC most often spreads to the pelvic lymph nodes (LNs) before becoming widely metastatic. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is strongly overexpressed in PC, making it an ideal target for imaging and therapy. 64 Cu-SAR-bisPSMA may offer several advantages over the currently approved PSMA positron emission tomography (PET) agents due to its bivalent structure (SAR-bisPSMA) and longer half-life of 64 Cu (12.7h vs. <2h for 18 F and 68 Ga). 64 Cu-SAR-bisPSMA has demonstrated higher tumor uptake (2-3x), prolonged retention and detection of additional PC lesions compared to approved PSMA agents. This Phase 3 diagnostic trial aims to establish the diagnostic performance of 64 Cu-SAR-bisPSMA PET to detect regional nodal metastases in men with high-risk PC. 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 endpoint is to assess the sensitivity and specificity of 64 Cu-SAR-bisPSMA PET to detect pelvic nodal metastases. Secondary objectives include assessment of safety and determining the positive and negative predictive value of 64 Cu-SAR-bisPSMA PET. A total of 383 patients will be enrolled. Standard of care (SOC) imaging will be acquired 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 (1-4h post-dose, same-day imaging) and on Day 2 (24±6h post-dose, next-day imaging). Patients will then 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 the presence of abnormal 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 PET result on the respective day independently (Day 1 and 2) matched against the SOT. The study is open for recruitment in sites in the United States and in Australia. Clinical trial information: NCT06056830 .