∙ Subjects must meet all of the following applicable inclusion criteria to participate in this study:

• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.

• Males 18 years of age and above.

• Histological or cytological proof of prostate adenocarcinoma or mixed adenocarcinoma/neuroendocrine tumors. Pure small cell of the prostate is not allowed.

• ECOG status of ≤ 2

• Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).

• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting. Subjects may have received more than 1 prior Androgen receptor signaling inhibitors (ARSI). Subjects may have had prior 177Lu-PSMA-617.

• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

• Normal organ function with acceptable initial laboratory values within 14 days of treatment start:

‣ WBC: ≥ 2,500/mcL

⁃ ANC: ≥ 1,500/mcL

⁃ Hemoglobin: ≥ 9 g/dL (transfusions are permitted)

⁃ Platelet count: ≥ 100,000/mcL

⁃ Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation

⁃ Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)

⁃ SGOT (AST): ≤ 3 x ULN

⁃ SGPT (ALT): ≤ 3 x ULN

⁃ Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases

⁃ Serum Albumin: ≥ 2.8 g/dL

⁃ Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 2 g

• Subjects must agree to use a medically acceptable method of birth control as outlined in the protocol

• HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count \> 350.