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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02923180
• Other study ID #: J1693
• Secondary ID: IRB00103776
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 14, 2017
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 33
• Est. completion date: December 2024
• Est. primary completion date: August 11, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 5a-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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Androgen Receptor (AR) Quantification	Mean staining percentage of AR in harvested prostate tissue, assessed by immunohistochemistry (IHC) staining for AR protein.	up to 3 years post-prostatectomy
Other	Tissue Androgen Concentrations	Concentration (picogram/3 mg) of testosterone and 5a-dihydrotestosterone (DHT) in prostate tissue.	up to 3 years post prostatectomy
Other	Global Expression Profiling of Tumor Tissues	Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.	up to 3 years post-prostatectomy
Other	IHC Analyses of CD137, CD16 and/or CD107A	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	up to 3 years post-prostatectomy
Other	TCR Repertoire	Fraction of peripherally expanded clones that are tumor associated for each participant.	3 years post-prostatectomy
Other	FC Receptor Genotyping	Number of participants with CD16A, CD32A, and CD32B on Fc receptor.	up to 3 years post-prostatectomy
Other	PBLs	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.	3 years post-prostatectomy
Other	B7-H3 Expression	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).	3 years post-prostatectomy
Other	PD-1, LAG3, and TIM3 Expression	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.	3 Years post-prostatectomy
Other	Quantify Antigen-spread	Number of participants with antigen-spread to on-target and off-target antigens.	3 years post-prostatectomy
Primary	Number of Participants With Treatment-related Adverse Events	Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0	2 years
Primary	Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate	Number of participants with undetectable Prostate Specific Antigen (PSA <0.1 ng/mL) at 12 months following radical prostatectomy	12 months
Secondary	Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients	Quantify markers of apoptosis in prostate tumor specimens of treated patients using TUNEL staining and expressed as the mean staining percentage in tumor tissue	up to 5 years post-prostatectomy
Secondary	Mean Staining Percentage of Markers of Cell Proliferation	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 years post-prostatectomy
Secondary	CD8+ T Cell Infiltration	Mean staining percentage of CD8+ T-cells in harvested prostate glands from treated patients	3 years post-prostatectomy
Secondary	PD-L1 Expression	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).	3 years post-prostatectomy
Secondary	Regulatory T Cell (Treg) Infiltration	Mean staining percentage of Treg cells in tumor tissue of treated patients, assessed through immunohistochemistry.	3 years post-prostatectomy
Secondary	CD4+ T Cell Infiltration	Mean staining percentage of CD4+ T-cells in tumor tissue of treated patients, assessed through immunohistochemistry.	3 years post-prostatectomy
Secondary	Natural Killer (NK) Cell Density	Mean staining percentage of NK cells in harvested prostate glands.	3 years post-prostatectomy
Secondary	Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue	Number of participants with positive or negative MGA271 detection in post-treatment prostate tumor specimens, as evaluated by IHC of fresh frozen sections.	3 years
Secondary	Pathological Complete Responses (pCR)	Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.	3 years
Secondary	PSA Response Rates	Number of participants with undetectable PSA (<0.1 ng/mL) at 3 months after prostatectomy.	3 months post-prostatectomy
Secondary	Time to PSA Recurrence	Median time (months) from prostatectomy to time when PSA is = 0.2 ng/mL. Estimated using Kaplan-Meier method.	up to 37 months post-prostatectomy
Secondary	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.	Day 50
Secondary	Number of Participants With PSA Percentage Decrease Prior to Radical Prostatectomy.	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.	50 Days