SECuRE: A dose escalation/expansion study to assess the anti-tumor efficacy of <sup>67</sup>Cu-SAR-bisPSMA in patients with metastatic castrate resistant prostate cancer.
Authors: Geoffrey Johnson, Eva Lengyelova, Luke Nordquist, Vikas Prasad, Monique Anderson, Othon Gervasio, Michelle Parker, Robert M. Miller, A. Oliver Sartor, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2024)

TPS5116 Background: Prostate cancer (PC) is common and despite recent advances in treatment options, patients with metastatic disease still have poor outcomes, warranting the development of new effective therapies in this setting. Prostate-specific membrane antigen (PSMA) is expressed in benign and malignant prostate tissues and luminal surface of salivary/lacrimal glands, small intestine and renal tubules. The double PSMA binding moiety of SAR-bisPSMA in 64 Cu-SAR-bisPSMA (imaging) and 67 Cu-SAR-bisPSMA (therapy) may offer advantages compared to currently used single-target PSMA agents. Clinical evidence demonstrated 2-3 times higher uptake of 64 Cu-SAR-bisPSMA compared to the single-target PSMA agent, 68 Ga-PSMA-11. Pre-clinical efficacy data of 67 Cu-SAR-bisPSMA in mice showed statistically significant tumor growth inhibition compared to the control group as well as a dose-dependent delay in eventual tumor regression in a PC xenograft study. These results led to the development of this clinical study, which aims to assess safety and anti-tumor efficacy of 67 Cu-SAR-bisPSMA in patients with metastatic castrate resistant PC (mCRPC). Methods: SECuRE is a phase I/IIa multi-center, open-label, non-randomized, dose-escalation and cohort expansion study of 64 Cu-SAR-bisPSMA and 67 Cu-SAR-bisPSMA (NCT04868604). mCRPC patients with progression, prior exposure to at least one androgen receptor pathway inhibitor, and positive 64 Cu-SAR-bisPSMA PET may be treated with 67 Cu-SAR-bisPSMA. This study is being conducted in 3 phases: a 64 Cu-SAR-bisPSMA Dosimetry Phase (n=6), a 67 Cu-SAR-bisPSMA Dose Escalation Phase (n=up to 24), and a 67 Cu-SAR-bisPSMA Cohort Expansion Phase (n=14). The primary and key secondary objectives include assessment of 64 Cu- and 67 Cu-SAR-bisPSMA safety and dosimetry, determining the maximum tolerated dose (MTD) or maximum feasible dose (MFD) and anti-tumor efficacy of 67 Cu-SAR-bisPSMA. The 67 Cu-SAR-bisPSMA dose levels investigated in the escalation phase include: 4 GBq (cohort 1, single dose), 8 GBq (cohort 2, single dose), 12 GBq (cohort 3, single dose) and up to 24 GBq across two doses (cohort 4, two doses at MTD or MFD). The Dose Expansion Phase of the study will allow the administration of up to 4 doses of 67 Cu-SAR-bisPSMA at the MTD/MFD. Response measurements include reduction in PSA levels, radiological progression-free survival, duration of response and overall survival. Radiological response will be assessed by RECIST V1.1 and PCWG3. At the time of submission of this abstract, no dose limiting toxicities have been observed to date in the first 3 cohorts. In the United States, 4 sites are active with additional sites in planning. Additional sites in the US and Australia are currently in start-up. Clinical trial information: NCT04868604 .