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

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: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Enoblituzumab; Other: Standard of Care

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: Interventional
• Enrollment (Estimated): 219
• Phase: Phase 2

Contacts and Locations

• Study Contact: 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: Claire Carter; Phone Number: 312-694-9001; Email: claire.carter@northwestern.edu
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Contact: Eugene Shenderov, MD, PhD; Phone Number: 410-502-7885; Email: eugene.shenderov@jhmi.edu
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Not yet recruiting
      • University of Minnesota
      • Principal Investigator: Christopher Warlick, MD
      • Contact: Simone Veum; Phone Number: 612-624-0937; Email: veum0015@umn.edu
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Paras Shah, MD
      • Contact: Paras Shah, MD; Phone Number: 507-466-0191; Email: Shah.Paras@mayo.edu
      • Contact: Urology Study Coordinator; Email: Biffert.Hosanna@mayo.edu
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Not yet recruiting
      • XCancer - Omaha, LLC
      • Principal Investigator: Luke Nordquist, MD
      • Contact: Emily Rosso; Phone Number: 402-991-8468; Email: emily@xcancer.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS)	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

Outcome Measure	Measure Description	Time Frame
Time to PSA recurrence	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 from randomization to death by any cause or date last known alive.	5 years post-prostatectomy
Metastasis-free survival	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	Undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.	3 months post-prostatectomy.
Recurrence free survival	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	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	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	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	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	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	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)	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

Outcome Measure	Measure Description	Time Frame
Quality of life assessment	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	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	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	Number of participants with CD16A, CD32A, and CD32B on Fc receptor.	Day 84
cfDNA, ctDNA, and tumor vesicle associated DNA/RNA prevalence	Number of participants with cfDNA, ctDNA, and tumor vesicle associated DNA/RNA biomarker.	Day 84
IHC Analyses of CD137, CD16 and/or CD107A	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	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	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	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	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	Number of participants with single cell RNA sequencing of tumor tissue in treated and untreated prostatectomies.	Day 84
PBL (peripheral blood lymphocytes)	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	Number of participants with cytokines and chemokines changes at baseline and pre-prostatectomy.	Day 84
PSMA dynamics	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	Number of participants with congruence in PSMA and conventional imaging.	90 day post-prostatectomy

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: MacroGenics
• Investigators: Principal Investigator: Eugene Shenderov, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: enoblituzumab
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID 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