Enfortumab Vedotin as Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria:

• Male subject aged ≥ 18 years.

• Histologically or cytologically confirmed adenocarcinoma of the prostate withoutsmall cell histology.

• Diagnosis of metastatic or locally advanced, inoperable disease that cannot betreated with definitive intent

• Castrate levels of testosterone as defined as < 50 ng/dL (1.73 nmol/L).

• Prior treatment with at least three or more cycles of taxane therapy (docetaxel orcabazitaxel).

Note: Docetaxel in the newly diagnosed metastatic setting and docetaxel rechallenge allowed.

• Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined assecond-generation antiandrogen therapies that include but are not limited toabiraterone acetate, enzalutamide, apalutamide, and darolutamide.

• Subject has received or refused therapies which have shown to improve overallsurvival and are recommended per National Comprehensive Cancer Network (NCCN)guidelines prior to enrollment in trial. Such agents include but are not limited todocetaxel, cabazitaxel, sipuleucel-T, olaparib, rucaparib, radium-223 and lutetium (177Lu) vipivotide tetraxetan depending on patient eligibility.

• Had disease progression on or after NHT prior to enrolling in the study.

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

• Adequate organ function as defined as:

• Hematologic:

• White blood cell count (WBC) ≥ 2000/mm3

• Absolute neutrophil count (ANC) ≥ 1500/mm3

• Platelet count ≥ 100,000/mm3

• Hemoglobin ≥ 9g/dL

• Hepatic:

• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) unlessthere is a known history of Gilbert's syndrome.

• Aspartate aminotransferase (AST)(SGOT)/Alanine aminotransferase (ALT)(SGPT) ≤ 5 × institutional ULN

• Renal:

• Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula:

• Highly effective contraception throughout the study as described in Section 7.4.

• Discontinued all previous treatments for cancer (except androgen-deprivation therapyand bone loss prevention treatment) 28 days prior to starting study therapy.

• Recovery to baseline or ≤ Grade 1 CTCAE v 5.0 from toxicities related to any priortreatments, unless Adverse Event(s) (AE(s)) are clinically non-significant and/orstable on supportive therapy as determined by the treating physician.

• Able to provide informed consent and willing to sign an approved consent form thatconforms to federal and institutional guidelines.

Exclusion Criteria:

• Prior or concurrent malignancy (other than adenocarcinoma of the prostate). Note:Patients with prior or concurrent malignancy whose natural history or treatment doesnot have the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are eligible for this trial as approved by the PrincipalInvestigator.

• The subject has an uncontrolled, significant intercurrent or recent illness thatwould preclude safe study participation.

• Clinically significant cardiovascular disease: myocardial infarction (<6 monthsprior to enrollment), unstable angina, congestive heart failure (> New York HeartAssociation Classification Class IIB) or a serious cardiac arrhythmia requiringmedication.

• Known HIV infection with a detectable viral load at the time of screening. Note:Patients on effective antiretroviral therapy with an undetectable viral load at thetime of screening are eligible for this trial.

• Known chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with adetectable viral load.

Note: Patients with an undetectable HBV viral load are eligible. Patients with an undetectable HCV viral load are eligible.

• Live attenuated vaccinations within ≤ 4 weeks of the first study therapy and whileon trial is prohibited.

• Known prior severe hypersensitivity to investigational product or any component inits formulations, including known severe hypersensitivity reactions to monoclonalantibodies (NCI CTCAE v5.0 Grade ≥ 3).

• Subjects taking prohibited medications as described in Section 6.3. A washout periodof prohibited medications for a period of at least 5 half-lives or as clinicallyindicated should occur prior to the start of treatment.