Sacituzumab Govitecan in Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Second Generation AR-Directed Therapy

Inclusion Criteria: * Documented histological or cytological evidence of adenocarcinoma of the prostate * Documented metastatic disease on bone scan and/or CT scans * Currently receiving enzalutamide, darolutamide, apalutamide and/or abiraterone. Subjects who have received combination enzalutamide/abiraterone or combination apalutamide/abiraterone as part of clinical trials are allowed but will need to be receiving only a single agent ARSI at the time of study enrollment. Subjects who have received any other therapeutic investigational product directed towards the AR or androgen biosynthesis are allowed. Prior treatment with first-generation AR antagonists (i.e., bicalutamide, nilutamide, flutamide) before second generation AR-directed therapy is allowed. * Demonstrated disease progression while on enzalutamide, darolutamide, apalutamide, and/or abiraterone. Progressive disease is defined by one or more of the following: * A rise in prostate specific antigen (PSA) on two successive determinations at least one week apart and PSA level ≥2 ng/mL * Soft-tissue progression defined by RECIST 1.1 * Bone disease progression defined by Prostate Cancer Working Group 2 (PCWG2) with ≥2 new lesions on bone scan * A minimum serum PSA level of ≥2 ng/mL that is rising based on the PCWG2 criteria * ≥18 y ears of age * Castrate levels of testosterone (\<50 ng/dL \[1.74 nmol/L\]) * Undergone orchiectomy, or have been on Luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, for at least 3 months prior to study treatment start. Subjects on LHRH agonists/antagonists must remain on these agents for the duration of the study * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 * Normal organ function with acceptable initial laboratory values within 30 days of study treatment start: * White Blood Cell Count (WBC) greater than or equal to 3000/μl * Absolute Neutrophil Count (ANC) greater than or equal to 1000/μl * Platelet count greater than or equal to100,000/μl * Hemoglobin (HGB) greater than or equal to 9 g/dL * Adequate hepatic function as evidenced by Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than 3X the upper limit of normal (ULN) and bilirubin levels of less than 2.0 mg/dl. * Adequate renal function as evidenced by serum creatinine of less than 2.0 mg/dL * Able to provide written informed consent, or have a legal representative provide written informed consent * Subjects must have a previously-acquired biopsy from a metastatic site available * Subjects must be willing and able (in the opinion of the treating physician) to undergo one research biopsy for the investigational component of this study * Subjects who have partners of child-bearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) during the treatment period and for 90 days after last dose of IMMU-132. Subjects must also agree to not donate sperm through 90 days following the last dose of IMMU-132. Exclusion Criteria: * Received prior cytotoxic chemotherapy such as docetaxel, cabazitaxel or platinum chemotherapy for metastatic prostate cancer, castration sensitive or castration resistant, within two years prior to study entry. Neoadjuvant chemotherapy is allowed. * Completed sipuleucel-T (Provenge ®) treatment within 30 days of study treatment start. * Received any therapeutic investigational agent within 2 weeks of study treatment start. * Received palliative radiotherapy within 4 weeks of study treatment start. * Received herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE, St. John's wort, selenium supplements, grape seed extract, etc.) within 4 weeks of study treatment start or plans to initiate treatment with these products/alternative therapies during the entire duration of the study. * Active central nervous system (CNS) metastases from prostate cancer. Subjects with treated epidural disease are eligible to enroll. Subjects with treated brain metastases can be included as long as \>4 weeks have elapsed since last treatment (radiotherapy or surgery) for brain metastases, the subject is neurologically and radiographically stable, and is not receiving corticosteroids for brain metastases. Subjects with untreated brain metastases are excluded. Brain imaging (CT or MRI) is not required at baseline if brain metastases are not clinically suspected. * A history within the last 3 years of another invasive malignancy (excluding non-melanoma skin cancer). * A QTcF interval of \>470 msec on the initial Screening ECG; if the Screening ECG QTcF interval is \>470 msec, then it may be repeated two more times, and if the mean QTcF of the 3 ECGs is ≤470 msec, the subject may be enrolled. * A history of clinically significant cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes and second degree or third degree atrioventricular heart block without a permanent pacemaker in place. Subjects with resolved or rate-controlled atrial fibrillation/atrial flutter are allowed. * NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction/acute coronary syndrome within the preceding 6 months. * Diabetes mellitus with more than 2 episodes of diabetic ketoacidosis in the 12 months preceding study treatment start. * Inadequately controlled hypertension (defined as blood pressure \>150mmHg systolic and/or \>100 mmHg diastolic despite antihypertensive medication) or any history of hypertensive crisis or hypertensive encephalopathy. * History of loss of consciousness or transient ischemic attack within 12 months before study treatment start. * Known active HIV, Hepatitis B, or Hepatitis C infections. * Any other medical, psychiatric, or social condition, including substance abuse, which in the opinion of the Investigator would preclude safe participation in the study.