Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer – a Pilot and Biomarker Study

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Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer

Condition: Prostate Cancer

Intervention:

  • Drug: Enoblituzumab

Purpose: This study evaluates the safety, anti-tumor effect, and immunogenicity of Enoblituzumab given before radical prostatectomy. All patients will receive Enoblituzumab for 6 weekly doses beginning 50 days prior to radical prostatectomy.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02923180

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Primary Outcome Measures:

  • Measure: Frequency, type, and severity of adverse events
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Estimation of PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) at 12 months following radical prostatectomy
  • Time Frame: 12 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Quantify markers of apoptosis in prostate tumor specimens of treated patients
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Markers of cell proliferation
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: CD8+ T cell infiltration
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: PD-L1 expression
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Regulatory T cell (Treg) infiltration
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: CD4+ T cell infiltration
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Mean NK cell density in tumor tissue from harvested prostate glands of patients.
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: FC Receptor Genotyping
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Sera for Immunoassays
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: PBLs
  • Time Frame: 30 days
  • Safety Issue:
  • Measure: TCR Repertoire
  • Time Frame: 90 days
  • Safety Issue:
  • Measure: B7-H3 expression
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Enoblituzumab (MGA271) drug distribution
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Tissue androgen concentrations
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Androgen receptor (AR) quantification
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Pathological complete responses (pCR)
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: PSA response rates
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Time to PSA recurrence
  • Time Frame: 3 Years
  • Safety Issue:
  • Measure: Assessment of Gleason grade change
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: Global expression profiling of pre and post treatment tumor tissue
  • Time Frame: 3 years
  • Safety Issue:
  • Measure: IHC analyses of CD137, CD16 and/or CD107A
  • Time Frame: 3 years
  • Safety Issue:

Estimated Enrollment: 32

Study Start Date: October 2016

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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
  • 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 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 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

Contact:

  • Emmanuel Antonarakis, MD
  • 410-502-7528

Location:

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Baltimore Maryland 21205 United States

View trial on ClinicalTrials.gov

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