Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Mitoguazone

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.

Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.

Enoblituzumab

Emmanuel Antonarakis, MD

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.

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.

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

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer

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

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

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

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

Fraction of peripherally expanded clones that are tumor associated for each participant.

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

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.

Number of participants with 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).

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.

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

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

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

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

Mean staining percentage of CD8+ T-cells in harvested prostate glands from treated patients

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).

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

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

Mean staining percentage of NK cells in harvested prostate glands.

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

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

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

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

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.

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.

MacroGenics

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Smoking History

Family History of Prostate Cancer

The Eastern Cooperative Oncology Group (ECOG) scale measures performance status, with scores ranging from 0-5; 0= fully active, performs without restriction, 1= can ambulate, but restricted in physically strenuous activity, 2= ambulatory and capable of self-care, but unable to work, active for \>50% of waking hours, 3= limited self-care, confined to bed or chair for \>50% of waking hours, 4= completely disabled, totally confined to bed/chair, 5= deceased

Eastern Cooperative Oncology Group (ECOG) performance status

Normal (BMI 18.5 - 24.9)

Overweight (BMI 25.0 - 29.9)

Obese (BMI ≥ 30.0)

Body-mass index (kg/m^2)

Grade Group 3: 4+3

Grade Group 4: 4+4

Grade Group 5: 4+5, 5+4, or 5+5

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). A higher grade group reflects a worse outcome.

Gleason Group / Gleason sum at biopsy

Number of subjects who received therapy for prostate cancer prior to enrollment.

Previous Therapy

Stage T3 is defined as cancer growth outside of the prostate and possibly spread to the seminal vesicles.

Stage T3 at initial diagnosis

Participants who met eligibility criteria

Dr. Emmanuel Antonarakis

Grade 1

Grade 2

Grade 3

Grade 4

Number of Participants With Treatment-related Adverse Events

PSA < 0.1 ng/mL

PSA ≥ 0.1 ng/mL

Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate

Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients

Only 30 of the 32 participants enrolled in the trial had evaluable tissue samples.

Mean Staining Percentage of Markers of Cell Proliferation

CD8+ T Cell Infiltration

PD-L1 Expression

Regulatory T Cell (Treg) Infiltration

CD4+ T Cell Infiltration

Natural Killer (NK) Cell Density

Positive

Negative

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.

Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue

Pathological Complete Responses (pCR)

PSA <0.1 ng/mL

PSA ≥0.1 ng/mL

PSA Response Rates

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.

Enoblituzumab: Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer	NCT02923180	Prostate Cancer	Enoblituzumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer	NCT02923180	Prostate Cancer	Enoblituzumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for enobilituzumab