Enoblituzumab in Treating Patients with Localized, Intermediate, or High-Risk Prostate Cancer
This pilot phase II trial studies the side effects of enoblituzumab in treating patients with localized, intermediate, or high-risk prostate cancer. Immunotherapy with enoblituzumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread.
Inclusion Criteria
- Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c–T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
- Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a Gleason sum of >= 7
- Radical prostatectomy has been scheduled at Johns Hopkins Hospital
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score >= 70%
- White blood cells (WBC) > 3,000 cells/mm^3
- Absolute neutrophil count (ANC) > 1,500 cells/mm^3
- Hemoglobin > 9.0 g/dL
- Platelet count > 100,000 cells/mm^3
- Serum creatinine < 1.5 x upper limit of normal (ULN)
- Serum bilirubin < 1.5 x ULN
- Alanine aminotransferase (ALT) < 3 x ULN
- Aspartate aminotransferase (AST) < 3 x ULN
- Alkaline phosphatase < 3 x ULN
- The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to study entry
- Willingness to provide written informed consent and Health Insurance Portability and Accountability Act (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 MGA271 until the time of prostatectomy
Exclusion Criteria
- Presence of known lymph node involvement or distant metastases
- 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 5alpha-reductase inhibitors
- Current use of systemic corticosteroids or use of systemic corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or chronic obstructive pulmonary disease [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, Sjogren 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 human immunodeficiency virus (HIV) and/or hepatitis B/C
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02923180.
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of enoblituzumab (MGA271) administered weekly x 6 (2 weeks prior to prostatectomy).
II. To evaluate the feasibility of administering MGA271 weekly x 6 (2 weeks prior to prostatectomy).
III. To estimate PSA0 response rate (undetectable PSA level < 0.1 ng/mL) at 12 months following radical prostatectomy. (Expansion cohort)
SECONDARY OBJECTIVES:
I. To quantify markers of apoptosis (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling [TUNEL] staining, caspase 3 staining, fragment crystallizable [Fc]gamma staining) in prostate tumor specimens of treated patients.
II. To quantify markers of cell proliferation (Ki-67) in prostate tumor specimens of treated patients.
III. To quantify the extent of cluster of differentiation (CD)8+ T cell infiltration into the prostate from harvested prostate glands of treated patients.
IV. To quantify the extent of PD-L1+ cell density in the prostate from harvested prostate glands of treated patients.
V. To quantify the extent of CD4+ T cell and regulatory T cells (Treg) infiltration into the prostate in prostate specimens of treated patients.
VI. To quantify CD8+/Treg and CD4+/Treg ratios in prostate specimens of treated patients.
VII. To quantify the extent of natural killer (NK) cell infiltration into the prostate from harvested prostate glands of treated patients.
VIII. Enoblituzumab (MGA271) intraprostatic drug distribution in treated patients.
IX. To evaluate the proportion of pathological complete responses (pCR) in prostate tumor specimens of treated patients.
X. To evaluate PSA response rates and the time-to-PSA-recurrence after radical prostatectomy in treated patients.
XI. To assess Gleason grade change post neoadjuvant enoblituzumab treatment, comparing prostatectomy Gleason sum to pre-treatment biopsy Gleason sum.
EXPLORATORY OBJECTIVES:
I. To quantify B7-H3 expression in pre and post treatment tumor tissue and correlate with tumor cell apoptosis and time to PSA-recurrence.
II. To quantify PD-L1, PD-1, lymphocyte-activation gene 3 (LAG3) and TIM3 in pre and post treatment tumor tissue.
III. Determination of Fc receptor genotype (CD16A, CD32A, CD32B).
IV. Immunohistochemistry (IHC) analyses of CD137, CD16 and/or CD107A across potential immune infiltrate following enoblituzumab (based on proposed mechanism of action [MoA]).
V. Tissue androgen concentrations.
VI. Androgen receptor (AR) quantification.
VII. Global expression profiling of pre and post treatment tumor tissue using single cell ribonucleic acid (RNA) sequencing, the immune NanoString immunopanel and/or microarrays.
VIII. T cell receptor (TCR) deep sequencing (Adaptive Biotech) testing hypothesis that successful anti-tumor response modulates TCR repertoire.
IX. Quantification of antigen-spread using ProtoArray analyses or similar analyses.
OUTLINE:
Patients receive enoblituzumab intravenously (IV) over 120 minutes on days 1, 8, 15, 22, 29, and 36. Patients then undergo radical prostatectomy on day 50.
After completion of study treatment, patients are followed up at 30 days, 90 days, every 3 months for 1 year, and every 6 months for 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorEmmanuel S. Antonarakis
- Primary IDJ1693
- Secondary IDsNCI-2016-02030, CRMS-64600, IRB00103776
- ClinicalTrials.gov IDNCT02923180