Neoadjuvant enoblituzumab for high-risk localized prostate cancer

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 is testing if a new drug called enoblituzumab can help men with high-risk localized prostate cancer before they have surgery, compared to the usual treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 219 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: Enoblituzumab, chemotherapy, immunotherapy, radiation
• Locations: 5 sites (Chicago, Illinois and 4 other locations)
• Trial ID: NCT06014255 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial evaluates the effectiveness and immune response of enoblituzumab administered before radical prostatectomy in men with high-risk localized prostate cancer. Participants will be randomly assigned to receive either enoblituzumab for 12 weeks or standard of care treatment. The study involves pre-treatment biopsies, imaging, and the collection of various biomarkers to assess treatment response. The trial aims to determine the anti-tumor effects of enoblituzumab compared to standard treatment protocols.

Who should consider this trial

Good fit: Ideal candidates are men aged 18 and older with high-risk localized prostate cancer, specifically those with a Gleason score of 8 or higher and no significant metastatic disease.

Not a fit: Patients with advanced prostate cancer involving lymph nodes, bone, or visceral organs may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for men with high-risk localized prostate cancer by enhancing tumor response before surgery.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in prostate cancer, indicating potential for success in this trial.

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).

Where this trial is running

Chicago, Illinois and 4 other locations

• Northewestern University — Chicago, Illinois, United States (Recruiting)
• Johns Hopkins Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Not_yet_recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• XCancer - Omaha, LLC — Omaha, Nebraska, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Eugene Shenderov — Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study coordinator: Carolyn Chapman GU oncology

Conditions Prostate Cancer; enoblituzumab