Trial of Neoadjuvant Enoblituzumab vs SOC in Men With High-Risk Localized Prostate Cancer (HEAT)

October 28, 2025 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Phase 2 Randomized Trial of Neoadjuvant Enoblituzumab Versus Standard of Care in Men With High-Risk Localized Prostate Cancer: The Help Elucidate & Attack Longitudinally (HEAT) Prostate Cancer Randomized Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
219

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Carolyn Chapman, RN
  • Phone Number: 443-287-7841

Study Contact Backup

  • Name: Carolyn Chapman GU oncology
  • Phone Number: 4109551239
  • Email: cchapma7@jhmi.edu

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northewestern University
        • Principal Investigator:
          • Ashley Ross, MD
        • Contact:
          • MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • Not yet recruiting
        • University of Minnesota
        • Principal Investigator:
          • Christopher Warlick, MD
        • Contact:
      • Rochester, Minnesota, United States, 55905
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Not yet recruiting
        • XCancer - Omaha, LLC
        • Principal Investigator:
          • Luke Nordquist, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

To be eligible for this study, patients must meet all of the following criteria:

  • Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs by CT or NM bone scan. N1 by PSMA allowed with up to 3 LNs each ≤1 cm. If there is no frank bone disease, but PSMA scan and CT scan are in discordance, then investigators will discuss.
  • Initial prostate biopsy, obtained within 3 months of enrollment, is available for central pathologic review, and is confirmed to show at least 3 positive cores (at least 1 core with at least 50% disease involvement with ≥4+3=7 disease) and a Gleason sum of ≥8 (or 4+3=7 with at least 1 additional high-risk feature such as PSA>20 or cT3)
  • Radical prostatectomy has been scheduled
  • Age ≥18 years
  • ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)

  • Adequate bone marrow, hepatic, and renal function:

    • WBC >3,000 cells/mm3
    • ANC >1,500 cells/mm3
    • Hemoglobin >9.0 g/dL
    • Platelet count >100,000 cells/mm3
    • Serum creatinine <1.5 × upper limit of normal (ULN)
    • Serum bilirubin <1.5 × ULN
    • ALT <3 × ULN
    • AST <3 × ULN
    • Alkaline phosphatase <3 × ULN
  • The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to study entry.
  • Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
  • Willingness to use barrier contraception from the time of first dose of Enoblituzumab (MGA271) until the time of prostatectomy.

Exclusion Criteria:

To be eligible for this study, patients should not meet any of the following criteria:

  • Presence of known lymph node involvement on CT (N1 by PSMA allowed with up to 3 LNs each ≤1 cm) or distant metastases by CT and NM bone scan
  • Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
  • Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
  • Prior immunotherapy/vaccine therapy for prostate cancer
  • Prior use of experimental agents for prostate cancer
  • Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors
  • Current use of systemic corticosteroids or use of systemic corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted as are other non-systemic steroids such as topical corticosteroids)
  • History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis)
  • History of malignancy within the last 3 years, with the exception of non-melanoma skin cancers and superficial bladder cancer
  • Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate
  • Known prior or current history of HIV and/or hepatitis B/C, with the exception of patients who have been successfully treated for hepatitis B/C (i.e. documented confirmation of cure at least 6 months after initial treatment).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Enoblituzumab
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.
Drug: Enoblituzumab
Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.
Other Names:
  • MGA271
Active Comparator: Standard of Care
Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.
Other: Standard of Care
Radical prostatectomy within 4-8 weeks of randomization.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recurrence-free survival (RFS)
Time Frame: 3 years post-prostatectomy
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.
3 years post-prostatectomy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to PSA recurrence
Time Frame: 5 years post-prostatectomy
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
5 years post-prostatectomy
Overall survival
Time Frame: 5 years post-prostatectomy
Time from randomization to death by any cause or date last known alive.
5 years post-prostatectomy
Metastasis-free survival
Time Frame: 5 years post-prostatectomy
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
5 years post-prostatectomy
PSA response
Time Frame: 3 months post-prostatectomy.
Undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.
3 months post-prostatectomy.
Recurrence free survival
Time Frame: 3 years from randomization
Measured by the number of participants who have not progressed at 36 months after randomization.
3 years from randomization
Number of participants with treatment-related adverse events
Time Frame: 90 days post-prostatectomy
Measured by the number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
90 days post-prostatectomy
Anti-tumor response (cleaved PARP staining and quantification of tumor cell apoptosis) to enoblituzumab versus SOC
Time Frame: Day 84
Measured by the number of participants with cleaved PARP staining and tumor cell apoptosis treated with enoblituzumab versus standard of care.
Day 84
Anti-tumor response (central pathological response graded according to standard criteria) to enoblituzumab versus SOC
Time Frame: Day 84
Measured by the number of participants with pathological response graded according to standard criteria treated with enoblituzumab versus standard of care.
Day 84
Assess the immune response (CD8 T cell infiltration into the tumor / peritumoral area) to enoblituzumab versus SOC
Time Frame: Day 84
Measured by the number of participants with CD8 T cell infiltration into the tumor / peritumoral area treated with enoblituzumab versus standard of care.
Day 84
Assess the immune response (CD8 Granzyme B) to enoblituzumab versus SOC
Time Frame: Day 84
Measured by the number of participants with CD8 Granzyme B treated with enoblituzumab versus standard of care.
Day 84
Change in number of participants with change in Gleason grade group change
Time Frame: Baseline and Day 84
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.
Baseline and Day 84
Pathological complete responses (pCR)
Time Frame: Day 84
Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.
Day 84

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality of life assessment
Time Frame: 6 months from randomization
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.
6 months from randomization
Quantify B7-H3 IHC expression
Time Frame: 5 years post-prostatectomy
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.
5 years post-prostatectomy
Quantify checkpoint IHC expression
Time Frame: Day 84
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.
Day 84
FC Receptor Genotyping
Time Frame: Day 84
Number of participants with CD16A, CD32A, and CD32B on Fc receptor.
Day 84
cfDNA, ctDNA, and tumor vesicle associated DNA/RNA prevalence
Time Frame: Day 84
Number of participants with cfDNA, ctDNA, and tumor vesicle associated DNA/RNA biomarker.
Day 84
IHC Analyses of CD137, CD16 and/or CD107A
Time Frame: Day 84
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
Day 84
Global Expression Profiling of Tumor Tissues
Time Frame: Day 84
Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.
Day 84
Global Metabolomic Profiling of Tumor Tissues
Time Frame: Day 84
Number of participants with changes in chemical processes involving metabolites, intermediates, cell metabolism, and other markers of activity versus exhaustion.
Day 84
Whole genome sequencing
Time Frame: Day 84
Number of participants with genomic differences in tumor tissue in treated and untreated prostatectomies.
Day 84
Long-read whole-genome sequencing analysis of DNA methylation
Time Frame: Day 84
Number of participants with DNA methylation of tumor tissue in treated and untreated prostatectomies using long-read whole-genome sequencing analysis.
Day 84
Single cell RNA sequencing of tumor tissue
Time Frame: Day 84
Number of participants with single cell RNA sequencing of tumor tissue in treated and untreated prostatectomies.
Day 84
PBL (peripheral blood lymphocytes)
Time Frame: 30 days post-prostatectomy
Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry.
30 days post-prostatectomy
Cytokines and chemokines
Time Frame: Day 84
Number of participants with cytokines and chemokines changes at baseline and pre-prostatectomy.
Day 84
PSMA dynamics
Time Frame: 90 day post-prostatectomy
Number of participants with changes in PSMA at baseline versus pre-prostatectomy versus 90 day-post-prostatectomy.
90 day post-prostatectomy
PSMA and Conventional imaging congruence
Time Frame: 90 day post-prostatectomy
Number of participants with congruence in PSMA and conventional imaging.
90 day post-prostatectomy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
MacroGenics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Eugene Shenderov, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 16, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 29, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • J2269
  • IRB00340678 (Other Identifier: JHM IRB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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