Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients

Inclusion Criteria: 1. Signed informed consent provided prior to any study-related procedure being performed; 2. Able to swallow and retain orally administered medication; 3. Male aged 18 years and older; 4. diagnosis of prostate carcinoma; 5. Men with either non-metastatic or metastatic CRPC are eligible; 6. Completed at least 4 or more weeks of prior continuous therapy with fixed stable dose enzalutamide, abiraterone or apalutamide prior to initiating study treatment (for Part 1), or with fixed stable dose enzalutamide (for Part 2), with no change in dose for at least 2 weeks prior to screening; 7. Serum testosterone level \<50 ng/dL (\<0.5 ng/mL, \<7.0 nmol/L). 8. ECOG performance status of 0 or 1; 9. Adequate baseline organ function; 10. Must have a QT interval corrected for heart rate according to Fridericia's formula (QTcF) \<470 milliseconds (msec) or \<480 msec with bundle branch block; 11. Male subject with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of screening until 3 months after the last dose of study medication; 12. Willing and able to comply with all protocol required visits and assessments. Exclusion Criteria: 1. Prior chemotherapy, radiation; 2. Prior malignancy other than CRPC. 3. Uncontrolled hypothyroidism, or TSH \>2.0 x ULN at screening. 4. Current use of or anticipated requirement of prohibited medication(s); 5. Any unresolved ≥grade 2 (per CTCAE v5.0) toxicity from previous anti-cancer therapy; 6. Previous history of difficulty swallowing capsules; 7. Known active infection requiring intravenous (IV); 8. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test ; 9. History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months prior to the start of study medication; 10. Poorly controlled hypertension; 11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 12. History or evidence of cardiovascular risk; known cardiac metastases; 13. Previous major surgery within 30 days prior to the start of study medication;