First, we performed a pilot study to determine a sub-optimal dose for PSMA ADC, using LuCaP 96CR, a model of CRPC with high PSMA expression that previously showed significant regressions in response to PSMA ADC….The effects of the PSMA ADC+ENZ combination were compared to PSMA ADC alone, ENZ alone, and placebo control....Most interestingly, a 12-week follow up and survival analysis show that all three treatments resulted in significant survival benefits but the combination therapy effects were the most pronounced resulting in ENZ vs PSMA ADC+ENZ HR = 0.09 with P = 0.0415 and with no deaths observed in the combination group....In summary, our results clearly indicate that the combination of PSMA ADC+ENZ possesses strong antitumor activity in the LuCaP 96CR model that is much more pronounced than the inhibitory effects of either agent alone.