• Histologically confirmed prostate adenocarcinoma that is progressive metastatic castration-resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry.

• Male participants who are at least 18 years of age on the day of signing informed consent.

• Castrate level of serum testosterone at study entry (\< 50 ng/dL). Note: Participants without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.

• Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide.

• Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must have recovered to Grade \<= 1 (except for any grade alopecia and grade \<= 2 neuropathy).

• Prior radiotherapy is allowed if the last radiotherapy treatment was greater than 2 weeks from start of study treatment on cycle 1, day 1 (C1D1). Note- Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.

• At least one Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) (PSMA PET) avid lesion on screening PSMA PET. A positive lesion is defined as uptake above background liver.

• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky \>= 70%).

• Demonstrates adequate organ function as defined below:

∙ Adequate bone marrow function:

⁃ absolute neutrophil count \>=1,500/microliter (mcL)

• platelets \>=100,000/mcL

• hemoglobin \> 9.0 g/dL

‣ Adequate hepatic function:

⁃ total bilirubin \<= 1.5 x upper limit of normal (ULN). In patients with known or suspected Gilbert's disease, direct bilirubin \<= ULN

• aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<= 2.5 x institutional ULN (\<= 5 x ULN in patients with liver metastases)

• alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<= 2.5 x institutional upper limit of normal (\<= 5 x ULN in patients with liver metastases)

‣ Adequate renal function:

⁃ creatinine \<= 1.5 x within institutional upper limit of normal OR

• creatinine clearance Glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2, calculated using the Cockcroft-Gault equation or 24 hour urine collection.

⁃ Participants must use appropriate methods of contraception during study treatment and for at least 6 months after last study treatment. Patients who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea \> 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential. Patients who have undergone vasectomy themselves should also be considered to be of childbearing potential. Acceptable methods of contraception include continuous total abstinence, or double-barrier method of birth control (e.g., condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception.

⁃ Participants must provide consent to comply to recommended radioprotection precautions during study.

⁃ Participants willing to undergo tumor biopsy and have at least one lesion safely accessible to tumor biopsy. Bone or soft tissue lesion is allowed.

⁃ Participants with previously treated brain metastases are eligible provided the following criteria are all met:

• Last treatment was \> 28 days prior to C1D1.

∙ No evidence of new/progressive brain metastases is observed on magnetic resonance imaging (MRI) obtained during screening window

∙ Patient is clinically stable without requirement of steroid treatment for at least 14 days prior to first dose of study treatment on C1D1.

⁃ Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

⁃ Ability to understand and the willingness to sign a written informed consent document.