AMPLIFY: A phase 3 study of ⁶⁴ Cu-SAR-bisPSMA positron emission tomography in participants with biochemical recurrence of prostate cancer.

TPS269 Background: Prostate cancer (PC) is the second most prevalent cancer in men globally. The need for improved PC imaging is reflected in a biochemical recurrence (BCR) rate of 20 to 40% after initial definitive therapy. Despite advances in technology, many patients will fail to have their recurrence accurately localized by imaging, especially at low PSA levels. Imaging modalities that are widely available and can accurately detect, monitor, and restage residual / recurrent loco-regional and metastatic disease are therefore highly desirable. 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 for PC due to the bivalent structure of SAR-bisPSMA and longer half-life of 64 Cu (t 1/2 = 12.7h), compared to the approved monovalent PSMA agents utilizing 18 F and 68 Ga (t 1/2 < 2h). Evidence has demonstrated prolonged tumor retention and 2-3x higher tumor uptake with detection of additional PC lesions using 64 Cu-SAR-bisPSMA compared to approved PSMA PET agents. Methods: AMPLIFY (NCT06970847) is a multi-center, single arm, open-label Phase 3 diagnostic performance study of 64 CuSAR-bisPSMA PET/CT in participants with a history of prostate adenocarcinoma and rising or detectable PSA after initial definitive treatment. The primary objective is to investigate the ability of 64 Cu-SAR-bisPSMA PET/CT to detect recurrence of PC, with co-primary endpoints of participant-level correct detection rate (CDR) and region-level positive predictive value (PPV) assessed independently for Day 1 and Day 2. Key secondary objectives include assessment of safety, participant-level PPV, and participant-level detection rate (DR). A total of 220 patients will be enrolled. All participants are required to have baseline conventional imaging. 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). Participants will then continue into the follow-up period to verify the 64 Cu-SAR-bisPSMA PET/CT findings. The 64 Cu-SAR-bisPSMA same- and next-day scans will be interpreted individually by a qualified local reader and 3 independent, blinded, central readers for the presence of abnormal 64 Cu-SAR-bisPSMA uptake. 64 Cu-SAR-bisPSMA PET/CT results on same- and next-day imaging will then be assessed against a composite Reference Standard by a central expert panel. The study is open for recruitment in the United States and Australia. Clinical trial information: NCT06970847 .