Pembrolizumab With Androgen Deprivation Therapy and Radiotherapy for the Treatment of Patients With High Risk Localized Prostate Cancer

NCT06528210 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00025491NCI-2024-04337
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests how well pembrolizumab along with standard of care androgen deprivation therapy, with bicalutamide and gonadotropin releasing hormone agonist, and radiotherapy for the treatment of patients with high risk prostate cancer that has not spread to other parts of the body (localized). A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Bicalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Gonadotropin-releasing hormone agonists prevent the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate cancer cells that need testosterone to grow. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving pembrolizumab with androgen deprivation therapy and radiotherapy may kill more tumor cells in patients with high risk localized prostate cancer.

Conditions

High Risk Prostate Carcinoma; Localized Prostate Adenocarcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Biopsy-complete response determined by post-treatment biopsy

  Will be defined as absence of detectable malignant cells in cores evaluated by established histologic techniques. An exact one-sided confidence interval will also be estimated and provided.

  From first dose of pembrolizumab Cycle 1 Day 1 to 6 months after Cycle 1 Day 1. Cycle length is 21 days.

• Incidence of adverse events

  Using Common terminology Criteria for Adverse Events (CTCAE) version 5.

  From first dose of pembrolizumab to 30 days after last dose of pembrolizumab

Secondary Outcomes (4)

• Post-treatment cancer detection rates in tumors by levels of PD-1 and PD-L1 expression

  From first dose of pembrolizumab to 6 months after Cycle 1 Day 1. Cycle length is 21 days.

• Health related quality of life

  From screening up to 5 years

• Incidence of grade 3 or higher immune related adverse events

  From first dose of pembrolizumab to 30 days after last dose of pembrolizumab

• Rate of biochemical relapse-free survival

  From enrollment of trial to 30 days post last dose of pembrolizumab

Study Arms (1)

Treatment (Pembrolizumab, ADT, radiotherapy)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 51 weeks in the absence of disease progression or unacceptable toxicity. Patients receive standard of care ADT with GNRH agonist (leuprolide, goserelin, triptorelin) or GNRH antagonist (relugolix, degarelix) for a total of 24 months, bicalutamide PO QD for 6 months or up to 24 months per the discretion of the treating physician and radiation therapy per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan and/or CT scan/MRI during screening and prostate biopsy and blood sample collection throughout the study.

Drug: Gonadotropin Releasing Hormone Agonists and Antagonists; Drug: Bicalutamide; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Other: Questionnaire Administration; Radiation: Radiation Therapy; Procedure: Bone Scan

Interventions

Gonadotropin Releasing Hormone Agonists and Antagonists DRUG

Given PO, IM, Sub-Q injection or Sub-Q implant

Also known as: GnRH Antagonist, Gonadotropin Releasing Hormone Inhibitor, Leuprolide, Goserelin, Triptorelin, Degarelix, Relugolix

Treatment (Pembrolizumab, ADT, radiotherapy)

Bicalutamide DRUG

Given PO

Also known as: Casodex, Cosudex, ICI 176,334, ICI 176334

Treatment (Pembrolizumab, ADT, radiotherapy)

Biopsy Procedure PROCEDURE

Undergo prostate biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (Pembrolizumab, ADT, radiotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Pembrolizumab, ADT, radiotherapy)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (Pembrolizumab, ADT, radiotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (Pembrolizumab, ADT, radiotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, Keytruda, Lambrolizumab, MK-3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar QL2107, QL2107, SCH 900475

Treatment (Pembrolizumab, ADT, radiotherapy)

Questionnaire Administration OTHER

Ancillary study

Treatment (Pembrolizumab, ADT, radiotherapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (Pembrolizumab, ADT, radiotherapy)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (Pembrolizumab, ADT, radiotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who are at least 18 years of age on the day of signing informed consent with newly diagnosed histologically confirmed non-metastatic adenocarcinoma of the prostate (regional spread as defined by National Comprehensive Cancer Network \[NCCN\] guidelines is allowed) will be enrolled in this study with any one of the following three high risk features:
• Gleason grade \> 8-10
• PSA \> 20 ng/ml

You may not qualify if:

• Participants must agree to use a contraception as detailed in the protocol during the treatment period and for at least 12 months plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the first dose of study intervention
• Absolute neutrophil count (ANC) ≥ 1500/µL. (Specimens must be collected within 10 days prior to the start of study intervention)
• Platelets ≥ 100 000/µL. (Specimens must be collected within 10 days prior to the start of study intervention)
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L. (Specimens must be collected within 10 days prior to the start of study intervention)
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Creatinine OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥ 30 mL/min for participant with creatinine levels \> 1.5 × institutional upper limit of normal (ULN). (Specimens must be collected within 10 days prior to the start of study intervention)
• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin ≤ 1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \> 1.5 × ULN. (Specimens must be collected within 10 days prior to the start of study intervention)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases). (Specimens must be collected within 10 days prior to the start of study intervention)
• International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. (Specimens must be collected within 10 days prior to the start of study intervention)
• Be willing to undergo a post-treatment prostate biopsy 6 months after completion of therapy on cycle 1 day 1 and optional re-biopsy at 12 months post cycle 1 day 1 if 6-month biopsy was positive for viable tumor
• PSA ≤ 100 ng/mL within 90 days of initiation of therapy. If PSA is repeated and drops below 100 ng/mL without treatment, enrollment will be permitted

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator
• Oregon Health and Science University: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; Leuprolide; Goserelin; Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix; bicalutamide; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; pembrolizumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Therapeutics; Physical Phenomena

Study Officials

• Arthur Hung

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: July 30, 2024
• Study Start: April 16, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 23, 2025

Record last verified: 2025-09