xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06014255</url>
    </required_header>
    <id_info>
      <org_study_id>J2269</org_study_id>
      <secondary_id>IRB00340678</secondary_id>
      <nct_id>NCT06014255</nct_id>
    </id_info>
    <brief_title>Trial of Neoadjuvant Enoblituzumab vs SOC in Men With High-Risk Localized Prostate Cancer</brief_title>
    <acronym>HEAT</acronym>
    <official_title>A Phase 2 Randomized Trial of Neoadjuvant Enoblituzumab Versus Standard of Care in Men With High-Risk Localized Prostate Cancer: The Help Elucidate &amp; Attack Longitudinally (HEAT) Prostate Cancer Randomized Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>MacroGenics</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study evaluates the efficacy, anti-tumor effect, and immunogenicity of neoadjuvant&#xD;
        enoblituzumab given before radical prostatectomy. Patients will be randomized to&#xD;
        enoblituzumab for a total of 12 weeks beginning 84 days before radical prostatectomy or&#xD;
        standard of care arms.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a multi-center, randomized, phase 2 study evaluating the efficacy, anti-tumor effect,&#xD;
        and immunogenicity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men&#xD;
        with high-risk localized prostate cancer. Patients will be recruited from the outpatient&#xD;
        Urology clinics and Multidisciplinary Prostate Cancer (&quot;Precision Medicine&quot;) Clinics at four&#xD;
        participating institutions including: Harvard/Dana-Farber Cancer Centers, Northwestern Lurie&#xD;
        Comprehensive Cancer Center, Mayo Clinic, and the University of Minnesota Masonic Cancer&#xD;
        Center. Eligible patients will undergo a pre-treatment prostate biopsy and conventional&#xD;
        imaging (CT and bone scan) as well as PSMA-PET and optional prostate MRI as per institutional&#xD;
        preferences. Patients who have N0 M0 disease by conventional imaging (N1 by PSMA allowed with&#xD;
        up to 3 LNs each ≤1 cm) will be trial eligible as long as concurrent hormonal or radiation&#xD;
        therapy is not given. Patients will then be randomized to enoblituzumab for a total of 12&#xD;
        weeks beginning 84 days prior to radical prostatectomy or SOC arms. Fourteen days after the&#xD;
        last treatment, prostate glands will be harvested at radical prostatectomy, and prostate&#xD;
        tissue will be examined for pathologic response and secondary pharmacodynamic/immunologic&#xD;
        endpoints as described herein. Pre-treatment, on-treatment, and post-treatment biomarkers of&#xD;
        response and resistance will be collected including: plasma, PBMC. Repeat PSMA scan will be&#xD;
        obtained prior to radical prostatectomy. Follow-up evaluation for adverse events will occur&#xD;
        30 and 90 days after surgery. Patients will then be followed by the patient's&#xD;
        urologists/oncologists according to standard institutional practices but will require PSA&#xD;
        evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">March 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">March 1, 2029</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Recurrence-free survival (RFS)</measure>
      <time_frame>3 years post-prostatectomy</time_frame>
      <description>Number of participants with RFS, defined as from randomization to any metastasis events, pelvic lymph node recurrence, detectable prostate-specific antigen (PSA) (PSA &gt;= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), or start of salvage or adjuvant therapy based on PSA criteria of 0.1 ng/mL or higher, or death for any cause, whichever occurs first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time to PSA recurrence</measure>
      <time_frame>5 years post-prostatectomy</time_frame>
      <description>Time from randomization to detectable prostate-specific antigen (PSA) (PSA &gt;= 0.2 ng/mL, confirmed by a second PSA of the same level or higher</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>5 years post-prostatectomy</time_frame>
      <description>Time from randomization to death by any cause or date last known alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metastasis-free survival</measure>
      <time_frame>5 years post-prostatectomy</time_frame>
      <description>Measured by the number of participants who achieve metastasis-free survival, defined as from randomization to date of first evidence of recorded metastases confirmed by imaging or histologic evidence, or death from any cause, or is censored at the date of last follow-up known without metastasis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSA response</measure>
      <time_frame>3 months post-prostatectomy.</time_frame>
      <description>Undetectable PSA (&lt;0.1 ng/mL) at 3 months after prostatectomy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Recurrence free survival</measure>
      <time_frame>3 years from randomization</time_frame>
      <description>Measured by the number of participants who have not progressed at 36 months after randomization.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with treatment-related adverse events</measure>
      <time_frame>90 days post-prostatectomy</time_frame>
      <description>Measured by the number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anti-tumor response (cleaved PARP staining and quantification of tumor cell apoptosis) to enoblituzumab versus SOC</measure>
      <time_frame>Day 84</time_frame>
      <description>Measured by the number of participants with cleaved PARP staining and tumor cell apoptosis treated with enoblituzumab versus standard of care.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anti-tumor response (central pathological response graded according to standard criteria) to enoblituzumab versus SOC</measure>
      <time_frame>Day 84</time_frame>
      <description>Measured by the number of participants with pathological response graded according to standard criteria treated with enoblituzumab versus standard of care.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assess the immune response (CD8 T cell infiltration into the tumor / peritumoral area) to enoblituzumab versus SOC</measure>
      <time_frame>Day 84</time_frame>
      <description>Measured by the number of participants with CD8 T cell infiltration into the tumor / peritumoral area treated with enoblituzumab versus standard of care.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assess the immune response (CD8 Granzyme B) to enoblituzumab versus SOC</measure>
      <time_frame>Day 84</time_frame>
      <description>Measured by the number of participants with CD8 Granzyme B treated with enoblituzumab versus standard of care.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in number of participants with change in Gleason grade group change</measure>
      <time_frame>Baseline and Day 84</time_frame>
      <description>Number of participants with change in Gleason grade group from pre-treatment biopsy vs. post-treatment biopsy. &quot;Downgrade&quot; refers to a net grade group change less than zero, &quot;upgrade&quot; refers to net grade group change more than zero, and &quot;no change&quot; refers to stable Gleason grade group. Gleason grade groups are defined as grade group 1 (Gleason score ≤ 6), grade group 2 (Gleason score 3+4=7), grade group 3 (Gleason score 4+3=7), grade group 4 (Gleason score 8), and grade group 5 (Gleason scores 9-10).The lower the grade group, the better the outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathological complete responses (pCR)</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Quality of life assessment</measure>
      <time_frame>6 months from randomization</time_frame>
      <description>Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate (Appendix F), FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline and 6 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.</description>
    </other_outcome>
    <other_outcome>
      <measure>Quantify B7-H3 IHC expression</measure>
      <time_frame>5 years post-prostatectomy</time_frame>
      <description>Number of participants with B7-H3 IHC expression in pre-treatment and post-treatment tumor tissue and correlation with tumor cell apoptosis and time to recurrence.</description>
    </other_outcome>
    <other_outcome>
      <measure>Quantify checkpoint IHC expression</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with checkpoint IHC expression (eg, PD-1, PD-L1, LAG3, and TIM3) in individual patient's pre and post treatment tumor tissue, and among all patient tumor tissue treated with enoblituzumab versus standard of care.</description>
    </other_outcome>
    <other_outcome>
      <measure>FC Receptor Genotyping</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with CD16A, CD32A, and CD32B on Fc receptor.</description>
    </other_outcome>
    <other_outcome>
      <measure>cfDNA, ctDNA, and tumor vesicle associated DNA/RNA prevalence</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with cfDNA, ctDNA, and tumor vesicle associated DNA/RNA biomarker.</description>
    </other_outcome>
    <other_outcome>
      <measure>IHC Analyses of CD137, CD16 and/or CD107A</measure>
      <time_frame>Day 84</time_frame>
      <description>CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue</description>
    </other_outcome>
    <other_outcome>
      <measure>Global Expression Profiling of Tumor Tissues</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.</description>
    </other_outcome>
    <other_outcome>
      <measure>Global Metabolomic Profiling of Tumor Tissues</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with changes in chemical processes involving metabolites, intermediates, cell metabolism, and other markers of activity versus exhaustion.</description>
    </other_outcome>
    <other_outcome>
      <measure>Whole genome sequencing</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with genomic differences in tumor tissue in treated and untreated prostatectomies.</description>
    </other_outcome>
    <other_outcome>
      <measure>Long-read whole-genome sequencing analysis of DNA methylation</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with DNA methylation of tumor tissue in treated and untreated prostatectomies using long-read whole-genome sequencing analysis.</description>
    </other_outcome>
    <other_outcome>
      <measure>Single cell RNA sequencing of tumor tissue</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with single cell RNA sequencing of tumor tissue in treated and untreated prostatectomies.</description>
    </other_outcome>
    <other_outcome>
      <measure>PBL (peripheral blood lymphocytes)</measure>
      <time_frame>30 days post-prostatectomy</time_frame>
      <description>Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>Cytokines and chemokines</measure>
      <time_frame>Day 84</time_frame>
      <description>Number of participants with cytokines and chemokines changes at baseline and pre-prostatectomy.</description>
    </other_outcome>
    <other_outcome>
      <measure>PSMA dynamics</measure>
      <time_frame>90 day post-prostatectomy</time_frame>
      <description>Number of participants with changes in PSMA at baseline versus pre-prostatectomy versus 90 day-post-prostatectomy.</description>
    </other_outcome>
    <other_outcome>
      <measure>PSMA and Conventional imaging congruence</measure>
      <time_frame>90 day post-prostatectomy</time_frame>
      <description>Number of participants with congruence in PSMA and conventional imaging.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">219</enrollment>
    <condition>Prostate Cancer</condition>
    <arm_group>
      <arm_group_label>Enoblituzumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard of Care</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Enoblituzumab</intervention_name>
      <description>Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.</description>
      <arm_group_label>Enoblituzumab</arm_group_label>
      <other_name>MGA271</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Standard of Care</intervention_name>
      <description>Radical prostatectomy within 4-8 weeks of randomization.</description>
      <arm_group_label>Standard of Care</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          To be eligible for this study, patients must meet all of the following criteria:&#xD;
  &#xD;
            -  Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0,&#xD;
               M0) without involvement of lymph nodes, bone, or visceral organs by CT or NM bone&#xD;
               scan. N1 by PSMA allowed with up to 3 LNs each ≤1 cm. If there is no frank bone&#xD;
               disease, but PSMA scan and CT scan are in discordance, then investigators will&#xD;
               discuss.&#xD;
  &#xD;
            -  Initial prostate biopsy, obtained within 3 months of enrollment, is available for&#xD;
               central pathologic review, and is confirmed to show at least 3 positive cores (at&#xD;
               least 1 core with at least 50% disease involvement with ≥4+3=7 disease) and a Gleason&#xD;
               sum of ≥8 (or 4+3=7 with at least 1 additional high-risk feature such as PSA&gt;20 or&#xD;
               cT3)&#xD;
  &#xD;
            -  Radical prostatectomy has been scheduled&#xD;
  &#xD;
            -  Age ≥18 years&#xD;
  &#xD;
            -  ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)&#xD;
  &#xD;
            -  Adequate bone marrow, hepatic, and renal function:&#xD;
  &#xD;
                 -  WBC &gt;3,000 cells/mm3&#xD;
  &#xD;
                 -  ANC &gt;1,500 cells/mm3&#xD;
  &#xD;
                 -  Hemoglobin &gt;9.0 g/dL&#xD;
  &#xD;
                 -  Platelet count &gt;100,000 cells/mm3&#xD;
  &#xD;
                 -  Serum creatinine &lt;1.5 × upper limit of normal (ULN)&#xD;
  &#xD;
                 -  Serum bilirubin &lt;1.5 × ULN&#xD;
  &#xD;
                 -  ALT &lt;3 × ULN&#xD;
  &#xD;
                 -  AST &lt;3 × ULN&#xD;
  &#xD;
                 -  Alkaline phosphatase &lt;3 × ULN&#xD;
  &#xD;
            -  The etiology of abnormal bilirubin and transaminase levels should be evaluated prior&#xD;
               to study entry.&#xD;
  &#xD;
            -  Willingness to provide written informed consent and HIPAA authorization for the&#xD;
               release of personal health information, and the ability to comply with the study&#xD;
               requirements (note: HIPAA authorization will be included in the informed consent)&#xD;
  &#xD;
            -  Willingness to use barrier contraception from the time of first dose of Enoblituzumab&#xD;
               (MGA271) until the time of prostatectomy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          To be eligible for this study, patients should not meet any of the following criteria:&#xD;
  &#xD;
            -  Presence of known lymph node involvement on CT (N1 by PSMA allowed with up to 3 LNs&#xD;
               each ≤1 cm) or distant metastases by CT and NM bone scan&#xD;
  &#xD;
            -  Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma,&#xD;
               small cell, and neuroendocrine tumors&#xD;
  &#xD;
            -  Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for&#xD;
               prostate cancer&#xD;
  &#xD;
            -  Prior immunotherapy/vaccine therapy for prostate cancer&#xD;
  &#xD;
            -  Prior use of experimental agents for prostate cancer&#xD;
  &#xD;
            -  Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors&#xD;
  &#xD;
            -  Current use of systemic corticosteroids or use of systemic corticosteroids within 4&#xD;
               weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted as are&#xD;
               other non-systemic steroids such as topical corticosteroids)&#xD;
  &#xD;
            -  History or presence of autoimmune disease requiring systemic immunosuppression&#xD;
               (including but not limited to: inflammatory bowel disease, systemic lupus&#xD;
               erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis,&#xD;
               hemolytic anemia, Sjögren syndrome, and sarcoidosis)&#xD;
  &#xD;
            -  History of malignancy within the last 3 years, with the exception of non-melanoma skin&#xD;
               cancers and superficial bladder cancer&#xD;
  &#xD;
            -  Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or&#xD;
               psychiatric illnesses that would make the patient a poor study candidate&#xD;
  &#xD;
            -  Known prior or current history of HIV and/or hepatitis B/C, with the exception of&#xD;
               patients who have been successfully treated for hepatitis B/C (i.e. documented&#xD;
               confirmation of cure at least 6 months after initial treatment).&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Eugene Shenderov</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Eugene Shenderov, MD, PhD</last_name>
      <phone>410-502-7885</phone>
      <email>eugene.shenderov@jhmi.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Carolyn Chapman, RN</last_name>
      <phone>443-287-7841</phone>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Johns Hopkins Sidney Kimmel Comprehensive Cancer Center</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21205</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>enoblituzumab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Prostatic Neoplasms</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06014255
  org study id: J2269
  secondary id: IRB00340678
  nct id: NCT06014255
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This study evaluates the efficacy, anti-tumor effect, and immunogenicity of neoadjuvant
        enoblituzumab given before radical prostatectomy. Patients will be randomized to
        enoblituzumab for a total of 12 weeks beginning 84 days before radical prostatectomy or
        standard of care arms.
  This is a multi-center, randomized, phase 2 study evaluating the efficacy, anti-tumor effect,
        and immunogenicity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men
        with high-risk localized prostate cancer. Patients will be recruited from the outpatient
        Urology clinics and Multidisciplinary Prostate Cancer ("Precision Medicine") Clinics at four
        participating institutions including: Harvard/Dana-Farber Cancer Centers, Northwestern Lurie
        Comprehensive Cancer Center, Mayo Clinic, and the University of Minnesota Masonic Cancer
        Center. Eligible patients will undergo a pre-treatment prostate biopsy and conventional
        imaging (CT and bone scan) as well as PSMA-PET and optional prostate MRI as per institutional
        preferences. Patients who have N0 M0 disease by conventional imaging (N1 by PSMA allowed with
        up to 3 LNs each ≤1 cm) will be trial eligible as long as concurrent hormonal or radiation
        therapy is not given. Patients will then be randomized to enoblituzumab for a total of 12
        weeks beginning 84 days prior to radical prostatectomy or SOC arms. Fourteen days after the
        last treatment, prostate glands will be harvested at radical prostatectomy, and prostate
        tissue will be examined for pathologic response and secondary pharmacodynamic/immunologic
        endpoints as described herein. Pre-treatment, on-treatment, and post-treatment biomarkers of
        response and resistance will be collected including: plasma, PBMC. Repeat PSMA scan will be
        obtained prior to radical prostatectomy. Follow-up evaluation for adverse events will occur
        30 and 90 days after surgery. Patients will then be followed by the patient's
        urologists/oncologists according to standard institutional practices but will require PSA
        evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Recurrence-free survival (RFS)
  time frame: 3 years post-prostatectomy
  description: Number of participants with RFS, defined as from randomization to any metastasis events, pelvic lymph node recurrence, detectable prostate-specific antigen (PSA) (PSA >= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), or start of salvage or adjuvant therapy based on PSA criteria of 0.1 ng/mL or higher, or death for any cause, whichever occurs first.
  measure: Time to PSA recurrence
  time frame: 5 years post-prostatectomy
  description: Time from randomization to detectable prostate-specific antigen (PSA) (PSA >= 0.2 ng/mL, confirmed by a second PSA of the same level or higher
  measure: Overall survival
  time frame: 5 years post-prostatectomy
  description: Time from randomization to death by any cause or date last known alive.
  measure: Metastasis-free survival
  time frame: 5 years post-prostatectomy
  description: Measured by the number of participants who achieve metastasis-free survival, defined as from randomization to date of first evidence of recorded metastases confirmed by imaging or histologic evidence, or death from any cause, or is censored at the date of last follow-up known without metastasis
  measure: PSA response
  time frame: 3 months post-prostatectomy.
  description: Undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.
  measure: Recurrence free survival
  time frame: 3 years from randomization
  description: Measured by the number of participants who have not progressed at 36 months after randomization.
  measure: Number of participants with treatment-related adverse events
  time frame: 90 days post-prostatectomy
  description: Measured by the number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
  measure: Anti-tumor response (cleaved PARP staining and quantification of tumor cell apoptosis) to enoblituzumab versus SOC
  time frame: Day 84
  description: Measured by the number of participants with cleaved PARP staining and tumor cell apoptosis treated with enoblituzumab versus standard of care.
  measure: Anti-tumor response (central pathological response graded according to standard criteria) to enoblituzumab versus SOC
  time frame: Day 84
  description: Measured by the number of participants with pathological response graded according to standard criteria treated with enoblituzumab versus standard of care.
  measure: Assess the immune response (CD8 T cell infiltration into the tumor / peritumoral area) to enoblituzumab versus SOC
  time frame: Day 84
  description: Measured by the number of participants with CD8 T cell infiltration into the tumor / peritumoral area treated with enoblituzumab versus standard of care.
  measure: Assess the immune response (CD8 Granzyme B) to enoblituzumab versus SOC
  time frame: Day 84
  description: Measured by the number of participants with CD8 Granzyme B treated with enoblituzumab versus standard of care.
  measure: Change in number of participants with change in Gleason grade group change
  time frame: Baseline and Day 84
  description: Number of participants with change in Gleason grade group from pre-treatment biopsy vs. post-treatment biopsy. "Downgrade" refers to a net grade group change less than zero, "upgrade" refers to net grade group change more than zero, and "no change" refers to stable Gleason grade group. Gleason grade groups are defined as grade group 1 (Gleason score ≤ 6), grade group 2 (Gleason score 3+4=7), grade group 3 (Gleason score 4+3=7), grade group 4 (Gleason score 8), and grade group 5 (Gleason scores 9-10).The lower the grade group, the better the outcome.
  measure: Pathological complete responses (pCR)
  time frame: Day 84
  description: Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.
  measure: Quality of life assessment
  time frame: 6 months from randomization
  description: Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate (Appendix F), FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline and 6 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.
  measure: Quantify B7-H3 IHC expression
  time frame: 5 years post-prostatectomy
  description: Number of participants with B7-H3 IHC expression in pre-treatment and post-treatment tumor tissue and correlation with tumor cell apoptosis and time to recurrence.
  measure: Quantify checkpoint IHC expression
  time frame: Day 84
  description: Number of participants with checkpoint IHC expression (eg, PD-1, PD-L1, LAG3, and TIM3) in individual patient's pre and post treatment tumor tissue, and among all patient tumor tissue treated with enoblituzumab versus standard of care.
  measure: FC Receptor Genotyping
  time frame: Day 84
  description: Number of participants with CD16A, CD32A, and CD32B on Fc receptor.
  measure: cfDNA, ctDNA, and tumor vesicle associated DNA/RNA prevalence
  time frame: Day 84
  description: Number of participants with cfDNA, ctDNA, and tumor vesicle associated DNA/RNA biomarker.
  measure: IHC Analyses of CD137, CD16 and/or CD107A
  time frame: Day 84
  description: CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue
  measure: Global Expression Profiling of Tumor Tissues
  time frame: Day 84
  description: Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.
  measure: Global Metabolomic Profiling of Tumor Tissues
  time frame: Day 84
  description: Number of participants with changes in chemical processes involving metabolites, intermediates, cell metabolism, and other markers of activity versus exhaustion.
  measure: Whole genome sequencing
  time frame: Day 84
  description: Number of participants with genomic differences in tumor tissue in treated and untreated prostatectomies.
  measure: Long-read whole-genome sequencing analysis of DNA methylation
  time frame: Day 84
  description: Number of participants with DNA methylation of tumor tissue in treated and untreated prostatectomies using long-read whole-genome sequencing analysis.
  measure: Single cell RNA sequencing of tumor tissue
  time frame: Day 84
  description: Number of participants with single cell RNA sequencing of tumor tissue in treated and untreated prostatectomies.
  measure: PBL (peripheral blood lymphocytes)
  time frame: 30 days post-prostatectomy
  description: Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry.
  measure: Cytokines and chemokines
  time frame: Day 84
  description: Number of participants with cytokines and chemokines changes at baseline and pre-prostatectomy.
  measure: PSMA dynamics
  time frame: 90 day post-prostatectomy
  description: Number of participants with changes in PSMA at baseline versus pre-prostatectomy versus 90 day-post-prostatectomy.
  measure: PSMA and Conventional imaging congruence
  time frame: 90 day post-prostatectomy
  description: Number of participants with congruence in PSMA and conventional imaging.
  arm group label: Enoblituzumab
  arm group type: Experimental
  description: Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
  arm group label: Standard of Care
  arm group type: Active Comparator
  description: Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.
  intervention type: Drug
  intervention name: Enoblituzumab
  description: Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.
  arm group label: Enoblituzumab
  other name: MGA271
  intervention type: Other
  intervention name: Standard of Care
  description: Radical prostatectomy within 4-8 weeks of randomization.
  arm group label: Standard of Care
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Eugene Shenderov
  role: Principal Investigator
  affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  last name: Eugene Shenderov, MD, PhD
  phone: 410-502-7885
  email: eugene.shenderov@jhmi.edu
  last name: Carolyn Chapman, RN
  phone: 443-287-7841
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Prostatic Neoplasms