Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).

2586Background: EC1169 is a small molecule drug conjugate designed to bind to prostate cancer (PCa) cells via prostate specific membrane antigen (PSMA) and, following endocytosis, to then release tubulysin B hydrazide (potent antimitotic). EC1169 administration to mice bearing PSMA-positive LNCaP and MDA PCa 2b xenografts has resulted in complete remissions and cures. EC0652, a novel tracer composed of a technetium-99m chelator and a PSMA-targeting moiety, is being developed to characterize whole body PSMA expression in real time. Rapid PSMA-specific uptake of 99mTc-EC0652 into tumor tissue and rapid clearance from normal tissue results in enhanced tumor-to-background ratios to localize PSMA expressing tissue on SPECT imaging. Methods: Key inclusion criteria are ECOG PS 0-1, adequate organ function, and a diagnosis of mCRPC. Patients (pts) undergo 99mTc-EC0652 SPECT scan prior to therapy. EC1169 is administered intravenously on 1 of 2 schedules every 21 days: 3 times weekly with 1 week off (TIW regimen), ...