Study of Sipuleucel-T With or Without Continuing New Hormonal Agents in Metastatic Prostate Cancer

Inclusion Criteria:

• Asymptomatic or minimally symptomatic metastatic prostate cancer, and the diagnosisof prostate cancer needs to be histologically confirmed by biopsy of the prostate ora metastatic lesion

• On combined ADT with LHRH analog and a NHA (enzalutamide, apalutamide orabiraterone) for metastatic prostate cancer with PSA progression, but no imagingprogression based on the prostate cancer working group (PCWG) 3 criteria

• Age 18 or above

• ECOG performance status 0 or 1

• Participants must have adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥1,000/mcL

• Platelets ≥100,000/mcL

• Hemoglobin > 10 g/dl

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• Creatinine 1.5 ≤ institutional ULN

• Human immunodeficiency virus (HIV)-infected participants on effectiveanti-retroviral therapy with undetectable viral load within 6 months are eligiblefor this trial.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Participants with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For participants with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load

• Participants with a prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment of sipuleucel-T are eligible for this trial

• No uncontrolled arrhythmia: patients with h/o myocardial infarction or history ofcongestive heart failure, need to have estimated left ventricle ejection fractionabove 40% either on echocardiogram or MUGA scan within 6 months of study enrollment

• Non-sterilized men who are sexually active with a female partner of childbearingpotential must agree to use adequate contraception prior to the study enrollment,and for the duration of study participation

• Ability to understand and the willingness to sign a written informed consentdocument

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 4 weeks prior toentering the study

• Prior treatment with sipuleucel-T

• Participants who have not recovered from adverse events (AEs) due to prioranti-cancer therapy (i.e., have residual toxicities > Grade 2).

• Participants who require > 50% dose reduction of NHA are excluded from the studyexcept for taking abiraterone at 250 mg with low fat food

• Documented brain metastases or liver metastases

• Treatment with any investigational compound within 30 days prior to the first doseof Sipuleucel-T

• Documented brain metastases or liver metastases

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome. HIV-positive participants on combinationantiretroviral therapy are ineligible because of the potential for sipluleucel-T tobe less clinically active in this population

• Inability to comply with protocol requirements