In this Phase 2 study, mCRPC patients with PSMA positive scans who progressed on prior ARTA and 1 or more cycle of taxanes, and are naïve to lutetium Lu 177 vipivotide tetraxetan, will be enrolled. Patients will be randomized in a 2:1 ratio to Arm A or Arm B.~Arm A receives ONC-392, 10 mg/kg, Q4W for up to 13 doses, plus lutetium Lu 177 vipivotide tetraxetan 7.4 GBq (200 mCi), Q6W for up to 6 doses.~Arm B receives lutetium Lu 177 vipivotide tetraxetan 7.4 GBq (200 mCi), Q6W for up to 6 doses.~The study is open-label and patients will be monitored throughout the study period for survival, disease progression, and adverse events.
The goal of this clinical trial is to examine the safety and efficacy of ONC-392 in combination with lutetium Lu 177 vipivotide tetraxetan in metastatic castration resistant prostate cancer patient who have disease progressed on androgen receptor pathway inhibition. The main questions it aims to answer are (1) whether it is safe to combine ONC-392 with lutetium Lu 177 vipivotide tetraxetan, (2) whether the combination increases the radiographic progression free survival (rPFS).~Participants will be randomized to two arms in 2:1 ratio. In experimental arm, they will be given ONC-392 10 mg/kg IV infusion, once every 4 weeks for up to 13 cycles or approximately one year, together with lutetium Lu 177 vipivotide tetraxetan 7.4 GBq IV, once every 6 weeks for up to 6 cycles. In active control arm, they will be given standard of care treatment with lutetium Lu 177 vipivotide tetraxetan 7.4 GBq IV, once every 6 weeks for up to 6 cycles.