Inclusion Criteria:  Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone Have radiographic or biochemical evidence of progression as determined by Investigator per standard criteria Have no known active or symptomatic central nervous system (CNS) disease  Prior therapy with abiraterone required and:  For Phase 1b only: up to 2 prior taxane-based chemotherapy regimens allowed for castration-resistant disease For Phase 2 only: Patients must not have received prior taxane-based chemotherapy for castrate-resistant disease or prior treatment with CDK inhibitors Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 Adequate bone marrow and organ function Eligible to receive enzalutamide Life expectancy of > 6 months  Exclusion Criteria:  History of seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma) Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs) radiation, or biological anti-cancer therapy within 14 days prior to first dose of NUV-422 and enzalutamide Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (or < 5 half-lives) for myelosuppressive agent prior to the first dose of NUV-422 and enzalutamide  Requires medications that are known to be strong inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide  For Phase 1b only: Requires medications that are known to be moderate inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide Prior therapy with enzalutamide, apalutamide, darolutamide, or investigational androgen receptor inhibitors Known allergy or hypersensitivity to enzalutamide