Overview

The purpose of this study is to see whether combining 2141-V11 with various standard treatments is an effective treatment approach for prostate cancer. 2141-V11 works by activating the immune system to find and kill cancer cells. Researchers will look at whether this treatment approach is able to completely get rid of cancer in participants, and they will check for the presence of minimal residual disease (MRD) in participants. MRD is a small number of cancer cells that can be detected in the body after treatment.

Eligibility

Inclusion Criteria:

• Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization) NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
• Male aged 18 years and above
• Serum testosterone of ≥150 ng/dL (Cohorts B and C) except for patients currently on ADT.
• Adequate bone marrow, hepatic, and renal function, as evidenced within 28 days prior to treatment start by:

        ANC ≥1500/µl (≥1000/µl if benign ethnic neutropenia) Hemoglobin ≥9 g/dL Platelet count
        ≥100,000/µl Creatinine Clearance Measure by Cockcroft-Gault Formula >45 mL/min Total
        Bilirubin ≤ 1.8 mg/dl (Note: In participants with Gilbert's syndrome, if total bilirubin is
        1.8 mg/dL, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN,
        participant may be eligible) SGOT (AST) ≤ 92.5 U/L SGPT (ALT) ≤ 137 U/L
          -  Participants must have a clinical T stage documented by the treating urologist/medical
             oncologist within 90 days prior to treatment start using the 8th edition American
             Joint Committee on Cancer (AJCC) staging system, recorded as the urologist's/medical
             oncologist's best clinical assessment of extent of local disease by digital rectal
             examination and/or available imaging studies such as transrectal ultrasound, CT scan,
             and/or MRI. (Applicable to Cohorts A, B and C).
          -  The primary tumor must be considered safely removable with gross negative margins
             based on initial imaging as determined by a urologist and documented as such.
          -  Agrees to use a condom (even men with vasectomies) and another effective method of
             birth control if he is having sex with a woman of childbearing potential or agrees to
             use a condom if he is having sex with a woman who is pregnant while on study drug and
             for 3 months following the last dose of study drug. Must also agree not to donate
             sperm during the study and for 3 months after receiving the last dose of study drug.
          -  Evidence of a targetable prostate lesion on prostate magnetic resonance imaging scan
        Exclusion Criteria:
        Participants that meet any of the criteria listed below will not be eligible for study
        entry:
          -  Prior prostate surgery, pelvic lymph node dissection, radiation therapy, or focal
             therapy as a treatment for prostate cancer or benign prostatic disease.
          -  Current ADT with GnRH antagonist/agonist and/or ARSI initiated >8 weeks prior to
             planned Cycle 1 of 2141-V11.
          -  Prior cytotoxic chemotherapy for prostate cancer
          -  Prior experimental therapy for prostate cancer within 30 days of planned Cycle 1 of
             2141-V11.
          -  Known brain, liver, lung or other visceral metastasis (with the exception of
             retroperitoneal and / or pelvic nodal metastases as per inclusion criteria)
          -  Prior prostate cancer metastasis-directed therapies other than described above.
          -  Currently active second malignancy or past medical history of malignancies diagnosed
             within the last 5 years that require active therapy and/or in remission with life
             expectancy of < 5 years, with the exception of resected non-melanoma skin cancers,
             non-muscle invasive bladder cancer, stage I head and neck cancer, or stage I
             colorectal cancer.
          -  Significant medical condition other than cancer, that would prevent consistent and
             compliant participation in the study that would, in the opinion of the investigator,
             make this protocol unreasonably hazardous including but not limited to:
               -  Any medical condition requiring a higher dose of corticosteroid than 5 mg
                  prednisone/prednisolone once daily
               -  Active infection requiring systemic therapy
               -  History of gastrointestinal disorders (medical disorders or extensive surgery)
                  that may interfere with the absorption of the study agents
               -  Uncontrolled hypertension (systolic blood pressure (BP) ≥ 160 mmHg or diastolic
                  BP ≥ 95 mmHg); participants with a history of hypertension are allowed provided
                  blood pressure is controlled by anti-hypertensive treatment (systolic BP <160
                  mmHg or diastolic BP <95 mmHg)
               -  Acute or chronic hepatitis B or hepatitis C infection. (Hepatitis B and C testing
                  are not mandatory)
          -  Presence of hepatitis B surface antibody is acceptable
               -  Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)
               -  Human immunodeficiency virus (HIV)-positive participants with 1 or more of the
                  following:
          -  Not receiving highly active anti-retroviral therapy.
          -  A change in anti-retroviral therapy within 6 months of the start of screening (except
             if, after consultation with the principal investigator (PI) / sponsor, a change is
             made to avoid a potential drug-drug interaction with the study drug).
          -  Receiving anti-retroviral therapy that may interfere with the study drug(s) (consult
             the PI / sponsor for review of medication prior to enrollment).
          -  CD4 count < 350 cell/mm3 at screening.
          -  An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months
             of the start of screening.
          -  HIV testing is not mandatory
               -  History of pituitary or adrenal dysfunction
               -  Clinically significant heart disease as evidenced by myocardial infarction, or
                  arterial thrombotic events in the past 6 months, severe or unstable angina, or
                  New York Heart Association (NYHA) Class III or IV heart disease or cardiac
                  ejection fraction measurement of < 50% at baseline, or clinically significant
                  ventricular arrhythmias within 6 months prior to treatment start.
               -  History of seizure or any condition that may predispose to seizure (including,
                  but not limited to prior stroke, transient ischemic attack or loss of
                  consciousness
                  ≤1 year prior to treatment start; brain arteriovenous malformation; or
                  intracranial masses such as schwannomas and meningiomas that are causing edema or
                  mass effect)
               -  History of an inflammatory bowel disease (Crohn's or ulcerative colitis)
               -  Any additional medications that investigators are concerned will affect the
                  response to immunotherapy.
          -  Use of any prohibited concomitant medications precluding safe treatment with ADT or an
             ARSI within 14 days prior to treatment start.
        Note: Medications known to lower the seizure threshold must be discontinued or substituted
        at least 4 weeks prior to treatment start
          -  Known allergies, hypersensitivity or intolerance to apalutamide, enzalutamide,
             daralutamide or GNRH agonist or GNRH antagonist
          -  Participants that cannot tolerate MRI