A Multi-arm, Phase 2 Study to Evaluate the Safety and Efficacy of Sacituzumab Govitecan in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Progressed on Second Generation AR-Directed Therapy

• 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 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 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 3 months prior to study treatment start. Subjects on LHRH agonists/antagonists must remain 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 of study 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 bilirubin levels 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 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.