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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02923180
• Collaborator: MacroGenics (Industry)
• Enrollment: 33
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 67.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Enoblituzumab	Phase 2

Detailed Description

This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity of neoadjuvant MGA271 given prior to radical prostatectomy in men with intermediate and high-risk localized prostate cancer. Eligible patients will receive MGA271 at a dose of 15mg/kg IV given weekly for 6 doses beginning 50 days prior to radical prostatectomy. 14 days after the last dose of MGA271, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and 90 days after surgery. Patients will then be followed by their urologists 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.

In Amendment 1, the study was expanded to enroll an additional 16 patients for a total of 32 patients to continue evaluating safety and better estimate the clinical benefit of Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) at 12 months following radical prostatectomy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer
• Actual Study Start Date: Feb 14, 2017
• Actual Primary Completion Date: Aug 11, 2020
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enoblituzumab Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.	Drug: Enoblituzumab; Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.; Other Names: MGA271

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-related Adverse Events [2 years]

   Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0

2. Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate [12 months]

   Number of participants with undetectable Prostate Specific Antigen (PSA <0.1 ng/mL) at 12 months following radical prostatectomy

Secondary Outcome Measures

1. Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients [up to 3 years post-prostatectomy]

   Quantify markers of apoptosis in prostate tumor specimens of treated patients using TUNEL staining and expressed as the mean staining percentage in tumor tissue

2. Markers of Cell Proliferation [up to 3 years post-prostatectomy]

   Quantify markers of cell proliferation in prostate tumor specimens of treated patients using Ki-67 staining and expressed by the mean staining percentage in tumor tissue

3. CD8+ T Cell Infiltration [up to 3 years post-prostatectomy]

   Number of CD8+ T-cells in harvested prostate glands from treated patients

4. PD-L1 Expression [up to 3 years post-prostatectomy]

   Mean staining percentage of PD-L1 in tumor tissue, assessed by immunohistochemistry (IHC) in the primary core specimens (pre-treatment) and the prostatectomy surgical specimens (post-treatment).

5. Regulatory T Cell (Treg) Infiltration [up to 3 years post-prostatectomy]

   Mean staining percentage of Treg cells in tumor tissue of treated patients, assessed through immunohistochemistry.

6. CD4+ T Cell Infiltration [up to 3 years post-prostatectomy]

   Mean staining percentage of CD4+ T-cells in tumor tissue of treated patients, assessed through immunohistochemistry.

7. Natural Killer (NK) Cell Density [up to 3 years post-prostatectomy]

   Mean staining percentage of NK cells in harvested prostate glands.

8. Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue [3 years]

   Number of participants with positive or negative MGA271 detection in post-treatment prostate tumor specimens, as evaluated by IHC of fresh frozen sections.

9. Pathological Complete Responses (pCR) [3 years]

   Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.

10. PSA Response Rates [3 months post-prostatectomy]

    Number of participants with undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.

11. Time to PSA Recurrence [up to 3 years post-prostatectomy]

    Median time from prostatectomy to time when PSA is ≥ 0.2 ng/mL. Estimated using Kaplan-Meier method.

12. Gleason Grade Group Change [Day 50]

    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.

13. Number of Participants With PSA Percentage Decrease Prior to Radical Prostatectomy. [50 Days]

    The PSA percentage change is calculated as the difference from the PSA at day 50 prior to prostatectomy and PSA at screening. A negative value of PSA percentage change ("PSA percentage < 0") indicates a decrease in PSA from screening, and a positive value (PSA percentage change >= 0) indicates an increase in PSA from screening.

Other Outcome Measures

1. Androgen Receptor (AR) Quantification [up to 3 years post-prostatectomy]

   Mean staining percentage of AR in harvested prostate tissue, assessed by immunohistochemistry (IHC) staining for AR protein.

2. Tissue Androgen Concentrations [up to 3 years post prostatectomy]

   Concentration (picogram/3 mg) of testosterone and 5α-dihydrotestosterone (DHT) in prostate tissue.

3. Global Expression Profiling of Tumor Tissues [up to 3 years post-prostatectomy]

   Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.

4. IHC Analyses of CD137, CD16 and/or CD107A [up to 3 years post-prostatectomy]

   CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue

5. TCR Repertoire [up to 3 years post-prostatectomy]

   Number of participants with changes in T-cell receptor (TCR) repertoire, assessed by TCR sequencing.

6. FC Receptor Genotyping [up to 3 years post-prostatectomy]

   Number of participants with CD16A, CD32A, and CD32B on Fc receptor.

7. PBLs [up to 3 years post-prostatectomy]

   Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry at treatment day 1 (pre-treatment), treatment day 36 (post-treatment), and 30 days post-prostatectomy.

8. B7-H3 Expression [up to 3 years post-prostatectomy]

   B7-H3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of B7-H3 in tumor tissue.

9. PD-1, LAG3, and TIM3 Expression [up to 3 Years post-prostatectomy]

   PD-1, LAG3, and TIM3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage in tumor tissue.

10. Quantify Antigen-spread [up to 3 years post-prostatectomy]

    Number of participants with antigen-spread to on-target and off-target antigens.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• MacroGenics

Investigators

• Principal Investigator: Emmanuel Antonarakis, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 8, 2021

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02923180
• Other Study ID Numbers: J1693; IRB00103776
• First Posted: Oct 4, 2016
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: enobilituzumab
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	33 subjects signed consent to be screened for eligibility. 1 subject signed consent, but did not meet the eligibility criteria to start the study (screen failure) 32 subjects received study treatment.

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Period Title: Overall Study
STARTED	32
COMPLETED	6
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (5.82)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	32 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	32 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.1%
White	30 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Smoking History (Count of Participants)
Yes	9 28.1%
No	23 71.9%
Family History of Prostate Cancer (Count of Participants)
Yes	7 21.9%
No	25 78.1%
ECOG performance status (Count of Participants)
0	31 96.9%
1	1 3.1%
Body-mass index (kg/m2) (Count of Participants)
Normal (BMI 18.5 - 24.9)	6 18.8%
Overweight (BMI 25.0 - 29.9)	14 43.8%
Obese (BMI ≥ 30.0)	12 37.5%
Gleason Group / Gleason sum at biopsy (Count of Participants)
Grade Group 3: 4+3	5 15.6%
Grade Group 4: 4+4	8 25%
Grade Group 5: 4+5, 5+4, or 5+5	19 59.4%
Previous Therapy (Count of Participants)
Count of Participants [Participants]	0 0%
Stage T3 at initial diagnosis (Count of Participants)
Yes	23 71.9%
No	9 28.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-related Adverse Events
Description	Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
Grade 1	31 96.9%
Grade 2	12 37.5%
Grade 3	4 12.5%
Grade 4	0 0%

2. Primary Outcome

Title	Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate
Description	Number of participants with undetectable Prostate Specific Antigen (PSA <0.1 ng/mL) at 12 months following radical prostatectomy
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
PSA < 0.1 ng/mL	21 65.6%
PSA ≥ 0.1 ng/mL	11 34.4%

3. Secondary Outcome

Title	Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients
Description	Quantify markers of apoptosis in prostate tumor specimens of treated patients using TUNEL staining and expressed as the mean staining percentage in tumor tissue
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Markers of Cell Proliferation
Description	Quantify markers of cell proliferation in prostate tumor specimens of treated patients using Ki-67 staining and expressed by the mean staining percentage in tumor tissue
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	CD8+ T Cell Infiltration
Description	Number of CD8+ T-cells in harvested prostate glands from treated patients
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	PD-L1 Expression
Description	Mean staining percentage of PD-L1 in tumor tissue, assessed by immunohistochemistry (IHC) in the primary core specimens (pre-treatment) and the prostatectomy surgical specimens (post-treatment).
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Regulatory T Cell (Treg) Infiltration
Description	Mean staining percentage of Treg cells in tumor tissue of treated patients, assessed through immunohistochemistry.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	CD4+ T Cell Infiltration
Description	Mean staining percentage of CD4+ T-cells in tumor tissue of treated patients, assessed through immunohistochemistry.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Natural Killer (NK) Cell Density
Description	Mean staining percentage of NK cells in harvested prostate glands.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue
Description	Number of participants with positive or negative MGA271 detection in post-treatment prostate tumor specimens, as evaluated by IHC of fresh frozen sections.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

The Overall Number of Participants Analyzed represents those evaluable for this outcome. Of the 32 participants who received study treatment, data from 2 subjects was not evaluable.

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	30
Positive	28 87.5%
Negative	2 6.3%

11. Secondary Outcome

Title	Pathological Complete Responses (pCR)
Description	Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
Count of Participants [Participants]	0 0%

12. Secondary Outcome

Title	PSA Response Rates
Description	Number of participants with undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.
Time Frame	3 months post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
PSA <0.1 ng/mL	26 81.3%
PSA ≥0.1 ng/mL	6 18.8%

13. Secondary Outcome

Title	Time to PSA Recurrence
Description	Median time from prostatectomy to time when PSA is ≥ 0.2 ng/mL. Estimated using Kaplan-Meier method.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Gleason Grade Group Change
Description	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	Day 50

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
Downgrade (< 0 net grade group change)	16 50%
No Change (= 0 net grade group change)	12 37.5%
Upgrade (> 0 net grade group change)	4 12.5%

15. Secondary Outcome

Title	Number of Participants With PSA Percentage Decrease Prior to Radical Prostatectomy.
Description	The PSA percentage change is calculated as the difference from the PSA at day 50 prior to prostatectomy and PSA at screening. A negative value of PSA percentage change ("PSA percentage < 0") indicates a decrease in PSA from screening, and a positive value (PSA percentage change >= 0) indicates an increase in PSA from screening.
Time Frame	50 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
Measure Participants	32
PSA percentage change < 0	16 50%
PSA percentage change >= 0	16 50%

16. Other Pre-specified Outcome

Title	Androgen Receptor (AR) Quantification
Description	Mean staining percentage of AR in harvested prostate tissue, assessed by immunohistochemistry (IHC) staining for AR protein.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Other Pre-specified Outcome

Title	Tissue Androgen Concentrations
Description	Concentration (picogram/3 mg) of testosterone and 5α-dihydrotestosterone (DHT) in prostate tissue.
Time Frame	up to 3 years post prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Other Pre-specified Outcome

Title	Global Expression Profiling of Tumor Tissues
Description	Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Other Pre-specified Outcome

Title	IHC Analyses of CD137, CD16 and/or CD107A
Description	CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Other Pre-specified Outcome

Title	TCR Repertoire
Description	Number of participants with changes in T-cell receptor (TCR) repertoire, assessed by TCR sequencing.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Other Pre-specified Outcome

Title	FC Receptor Genotyping
Description	Number of participants with CD16A, CD32A, and CD32B on Fc receptor.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Other Pre-specified Outcome

Title	PBLs
Description	Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry at treatment day 1 (pre-treatment), treatment day 36 (post-treatment), and 30 days post-prostatectomy.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Other Pre-specified Outcome

Title	B7-H3 Expression
Description	B7-H3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of B7-H3 in tumor tissue.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Other Pre-specified Outcome

Title	PD-1, LAG3, and TIM3 Expression
Description	PD-1, LAG3, and TIM3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage in tumor tissue.
Time Frame	up to 3 Years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Other Pre-specified Outcome

Title	Quantify Antigen-spread
Description	Number of participants with antigen-spread to on-target and off-target antigens.
Time Frame	up to 3 years post-prostatectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	2 years
Arm/Group Title	Enoblituzumab
Arm/Group Description	Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.
All Cause Mortality
	Enoblituzumab
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Serious Adverse Events
	Enoblituzumab
	Affected / at Risk (%)	# Events
Total	3/32 (9.4%)
Blood and lymphatic system disorders
Ascites	1/32 (3.1%)
Cardiac disorders
Pericardial Effusion	1/32 (3.1%)
Cardiac Disorders - Other, Non-ST-Elevation, Myocardial Infarction	1/32 (3.1%)
Atrial Fibrillation	1/32 (3.1%)
Pericarditis	1/32 (3.1%)
Myocarditis	1/32 (3.1%)
Immune system disorders
Infusion related reaction	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Enoblituzumab
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Anemia	5/32 (15.6%)	7
Cardiac disorders
Atrial fibrillation	1/32 (3.1%)	1
Pericarditis	1/32 (3.1%)	2
Myocarditis	1/32 (3.1%)	2
Pericardial effusion	1/32 (3.1%)	2
Hypotension	2/32 (6.3%)	2
Eye disorders
Right eye stye	1/32 (3.1%)	1
Eye pain	2/32 (6.3%)	2
Gastrointestinal disorders
Abdominal pain	5/32 (15.6%)	5
Vomiting	5/32 (15.6%)	5
Constipation	2/32 (6.3%)	2
Nausea	8/32 (25%)	10
Diarrhea	2/32 (6.3%)	2
Dry mouth	1/32 (3.1%)	1
Ascites	1/32 (3.1%)	1
Abdominal distension	1/32 (3.1%)	1
Gastroesophageal reflux disease	1/32 (3.1%)	1
Bloating	1/32 (3.1%)	1
Dysgeusia	1/32 (3.1%)	1
General disorders
Fatigue	23/32 (71.9%)	34
Flu like symptoms	13/32 (40.6%)	17
Edema limbs	4/32 (12.5%)	5
Chills	9/32 (28.1%)	10
Fever	8/32 (25%)	9
Infusion related reaction	6/32 (18.8%)	7
Immune system disorders
Allergic reaction	1/32 (3.1%)	2
Infections and infestations
Upper respiratory infection	4/32 (12.5%)	4
Injury, poisoning and procedural complications
Bruising	2/32 (6.3%)	2
Seroma	3/32 (9.4%)	3
Bladder anastomotic leak	1/32 (3.1%)	1
Investigations
White blood cell decreased	1/32 (3.1%)	1
Creatinine increased	3/32 (9.4%)	7
CD4 lymphocytes decreased	1/32 (3.1%)	1
Aspartate aminotransferase increased	1/32 (3.1%)	1
Alanine aminotransferase increased	1/32 (3.1%)	1
Serum amylase increased	4/32 (12.5%)	7
Lipase increased	2/32 (6.3%)	4
Weight gain	2/32 (6.3%)	2
Blood bilirubin increased	2/32 (6.3%)	2
Platelet count decreased	1/32 (3.1%)	1
Metabolism and nutrition disorders
Hyponatremia	1/32 (3.1%)	1
Hypocalcemia	3/32 (9.4%)	3
Hypoalbuminemia	1/32 (3.1%)	1
Anorexia	4/32 (12.5%)	4
Hyperkalemia	1/32 (3.1%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	9/32 (28.1%)	9
Arthralgia	6/32 (18.8%)	8
Neck pain	1/32 (3.1%)	1
Left knee weakness	1/32 (3.1%)	1
Back pain	3/32 (9.4%)	4
Left meniscus tear/injury	1/32 (3.1%)	1
Nervous system disorders
Headache	13/32 (40.6%)	14
Dizziness	2/32 (6.3%)	2
Paresthesia	2/32 (6.3%)	2
Renal and urinary disorders
Urinary incontinence	31/32 (96.9%)	31
Erectile dysfunction	12/32 (37.5%)	12
Dysuria	3/32 (9.4%)	3
Urinary retention	2/32 (6.3%)	3
Acute kidney injury	1/32 (3.1%)	1
Leukocyturia	1/32 (3.1%)	1
Hemoglobinuria	1/32 (3.1%)	1
Hematuria	2/32 (6.3%)	2
Discolored urine	1/32 (3.1%)	1
Urinary frequency	2/32 (6.3%)	3
Urinary tract infection	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/32 (12.5%)	6
Nasal congestion	5/32 (15.6%)	5
Cold symptoms	1/32 (3.1%)	1
Postnasal drip	1/32 (3.1%)	1
Sore throat	1/32 (3.1%)	1
Dyspnea	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
IV infiltration	1/32 (3.1%)	1
Rash maculo-papular	3/32 (9.4%)	4
Pruritus	2/32 (6.3%)	2
Skin infection	1/32 (3.1%)	1
Incision site tenderness and erythema	1/32 (3.1%)	1
Surgical and medical procedures
Loss of dental filling	1/32 (3.1%)	1
Vascular disorders
Lymphocele	1/32 (3.1%)	1
Flushing	1/32 (3.1%)	1
Tachycardia	1/32 (3.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.