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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
219
Enoblituzumab 15mg/kg IV (in the vein) every 2 weeks for 12 weeks prior to radical prostatectomy on day 84.
Radical prostatectomy within 4-8 weeks of randomization.
Northewestern University
Chicago, Illinois, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
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.
Time frame: 3 years post-prostatectomy
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
Time frame: 5 years post-prostatectomy
Overall survival
Time from randomization to death by any cause or date last known alive.
Time frame: 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
Time frame: 5 years post-prostatectomy
PSA response
Undetectable PSA (\<0.1 ng/mL) at 3 months after prostatectomy.
Time frame: 3 months post-prostatectomy.
Recurrence free survival
Measured by the number of participants who have not progressed at 36 months after randomization.
Time frame: 3 years from randomization
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XCancer - Omaha, LLC
Omaha, Nebraska, United States
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 84