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

NCT ID: NCT06014255

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-16
• Study Completion Date: 2029-03-01

Brief Summary

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Enoblituzumab

Intervention Type: DRUG

Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.

Standard of Care

Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

Radical prostatectomy within 4-8 weeks of randomization.

Interventions

Enoblituzumab

Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.

Intervention Type: DRUG

Standard of Care

Radical prostatectomy within 4-8 weeks of randomization.

Intervention Type: OTHER

Other Intervention Names

MGA271

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

MacroGenics

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eugene Shenderov

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Northewestern University

Chicago, Illinois, United States

Site Status: RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: NOT_YET_RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status: RECRUITING

XCancer - Omaha, LLC

Omaha, Nebraska, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Carolyn Chapman GU oncology

Role: CONTACT

cchapma7@jhmi.edu

4109551239

Carolyn Chapman, RN

Role: CONTACT

443-287-7841

Facility Contacts

Claire Carter

Role: primary

claire.carter@northwestern.edu

312-694-9001

MD

Role: backup

Eugene Shenderov, MD, PhD

Role: primary

eugene.shenderov@jhmi.edu

410-502-7885

Simone Veum

Role: primary

veum0015@umn.edu

612-624-0937

Paras Shah, MD

Role: primary

Shah.Paras@mayo.edu

507-466-0191

Urology Study Coordinator

Role: backup

Biffert.Hosanna@mayo.edu

Emily Rosso

Role: primary

emily@xcancer.com

402-991-8468

Other Identifiers

IRB00340678

Identifier Type: OTHER

Identifier Source: secondary_id

J2269

Identifier Type: -

Identifier Source: org_study_id