177Lu-J591 and 177Lu-PSMA-617 Combination for mCRPC

This is an open-label, single-center Phase I dose-escalation study designed to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of combination of 177Lu-J591 and 177Lu-PSMA-617 in a two-week dose-fractionation regimen. 177Lu-J591 will be given at a moderate dose previously demonstrated to be safe x2 infusions two weeks apart. For 177Lu-PSMA-617 the dose escalation will start at 3.7 GBq (100 mCi) and escalate in increments of 1.85 GBq (50 mCi) for each dose to a planned maximum of 9.25 GBq (250 mCi) x2 doses, 2 weeks apart. Should there be unacceptable toxicity at the initial dose level, we will de-escalate to dose level -1 (1.85 GBq / 50 mCi per dose). After the phase I study has established a MTD, the Phase II, single-arm trial will start. Patients must have documented progressive metastatic CRPC disease based on Prostate Cancer Working Group 3 (PCWG3) criteria in order to be eligible for enrollment. Upon meeting the inclusion and exclusion criteria and signing the informed consent and HIPPA form, subjects will undergo the screening. As part of the screening, subjects will get a single dose of 68Ga-PSMA-HBED-CC and will have a PET/CT. Nuclear Medicine physician(s) will review the PET/CT scans to document PSMA expression at tumor site(s). Subjects will have Lutetium-177 Planar/SPECT Imaging on Day 8 (±1 day) after the first dose of 177Lu-J591 + 177Lu-PSMA-617. Optimal images will be performed on selected consenting subjects between the initial treatment visit #1 on Day 1 and Day 4 and prior to treatment visit #2 on D15 ±1. Subjects will be closely monitored for AEs (weekly x2 weeks, then every 2 weeks for one month, at 8 and 12 weeks, and then every 4 weeks for next 3 months). Upon completion of investigational treatment with dose-fractionation regimen of the combination of 177Lu-J591 + 177Lu-PSMA-617, subjects will undergo 68Ga-PSMA-HBED-CC injection and same day PET/CT at the end of study visit to document treatment response. Subsequently survival data and additional treatment(s) information will be captured from their routine Standard of care (SOC) visits. .