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 combinationapalutamide/abiraterone as part of clinical trials are allowed but will need to bereceiving only a single agent ARSI at the time of study enrollment. Subjects who havereceived any other therapeutic investigational product directed towards the AR orandrogen biosynthesis are allowed. Prior treatment with first-generation ARantagonists (i.e., bicalutamide, nilutamide, flutamide) before second generationAR-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 PSA on two successive determinations at least one week apart and PSAlevel ≥2 ng/mL
• Soft-tissue progression defined by RECIST 1.1
• Bone disease progression defined by 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 LHRH agonists or antagonists, for at least 3months prior to study treatment start. Subjects on LHRH agonists/antagonists mustremain on these agents for the duration of the study
• ECOG Performance Status of 0-1
• Normal organ function with acceptable initial laboratory values within 30 days ofstudy treatment start:
• WBC ≥3000/μl
• ANC ≥1000/μl
• Platelet count ≥100,000/μl
• HGB ≥9 g/dL
• Adequate hepatic function as evidenced by AST/ALT levels <3X the ULN and bilirubinlevels of <2.0 mg/dl.
• Adequate renal function as evidenced by serum creatinine of <2.0 mg/dL
• Able to provide written informed consent, or have a legal representative providewritten 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) toundergo one research biopsy for the investigational component of this study
• Subjects who have partners of child-bearing potential must be willing to use at leasttwo forms of effective birth control (one form must be a barrier method) during thetreatment period and for 90 days after last dose of IMMU-132. Subjects must also agreeto not donate sperm through 90 days following the last dose of IMMU-132.

Exclusion Criteria:

• Received prior cytotoxic chemotherapy such as docetaxel, cabazitaxel or platinumchemotherapy for metastatic prostate cancer, castration sensitive or castrationresistant, 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 treatmentstart.
• Received palliative radiotherapy within 4 weeks of study treatment start.
• Received herbal products or alternative therapies that may decrease PSA levels or thatmay 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 ofstudy treatment start or plans to initiate treatment with these products/alternativetherapies during the entire duration of the study.
• Active CNS metastases from prostate cancer. Subjects with treated epidural disease areeligible to enroll. Subjects with treated brain metastases can be included as long as >4 weeks have elapsed since last treatment (radiotherapy or surgery) for brainmetastases, the subject is neurologically and radiographically stable, and is notreceiving corticosteroids for brain metastases. Subjects with untreated brainmetastases are excluded. Brain imaging (CT or MRI) is not required at baseline ifbrain metastases are not clinically suspected.
• A history within the last 3 years of another invasive malignancy (excludingnon-melanoma skin cancer).
• A QTcF interval of >470 msec on the initial Screening ECG; if the Screening ECG QTcFinterval is >470 msec, then it may be repeated two more times, and if the mean QTcF ofthe 3 ECGs is ≤470 msec, the subject may be enrolled.
• A history of clinically significant cardiac arrhythmias including ventriculartachycardia, ventricular fibrillation, torsades de pointes and second degree or thirddegree atrioventricular heart block without a permanent pacemaker in place. Subjectswith resolved or rate-controlled atrial fibrillation/atrial flutter are allowed.
• NYHA Class III or IV congestive heart failure, unstable angina, myocardialinfarction/acute coronary syndrome within the preceding 6 months.
• Diabetes mellitus with more than 2 episodes of diabetic ketoacidosis in the 12 monthspreceding study treatment start.
• Inadequately controlled hypertension (defined as blood pressure >150mmHg systolicand/or >100 mmHg diastolic despite antihypertensive medication) or any history ofhypertensive crisis or hypertensive encephalopathy.
• History of loss of consciousness or transient ischemic attack within 12 months beforestudy treatment start.
• Known active HIV, Hepatitis B, or Hepatitis C infections.
• Any other medical, psychiatric, or social condition, including substance abuse, whichin the opinion of the Investigator would preclude safe participation in the study.