Pembro With Radiation With or Without Olaparib

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexMale
• Healthy volunteersNo

You may be able to join if

• Male participants with histologically confirmed adenocarcinoma of the prostate
• High-risk / very high-risk status per NCCN guidelines
• ECOG performance status 0 to 1
• Regional lymph nodes are allowed.
• Agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period.
• Ability to understand and the willingness to sign a written informed consent document.
• Adequate organ and marrow function
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation is ≤90 days prior to the date of registration
• Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.

You cannot join if

• Prior hormonal therapy with LHRH agonists (e.g., Lupron) and LHRH antagonists (e.g., Degarelix)for prostate cancer continuously for more than 90-days prior to study enrollment.
• Prior radiation to the prostate or pelvic nodes radiation.
• Previous or major surgery (colorectal anastomosis, total cystectomy, etc.).
• History of Ulcerative proctitis.
• Concurrent active, additional malignancy in the last 2 years.
• Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
• Patients with M1 disease

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

boron-dipyrromethene-modified olaparib fluorescent imaging agent. A poly (ADP-ribose) polymerase type 1 (PARP1) fluorescence imaging agent based on the PARP1 inhibitor olaparib, in which the cyclopropane group of olaparib is replaced by the green fluorescent dye boron-dipyrromethene (BODIPY) fluorophore (FL), with potential fluorescent imaging activity. Upon administration of the fluorescent PARP1 inhibitor PARPi-FL, the olaparib binding moiety specifically targets and binds to PARP1, which is often overexpressed on cancer cells. Upon fluorescent imaging, the PARP1-expressing cancer cells can be visualized. PARP1, the nuclear enzyme that catalyzes post-translational ADP-ribosylation of nuclear proteins, is activated by single-strand (SS) DNA breaks and overexpressed in certain tumor cells; it plays a key role in DNA repair, tumor cell resistance and survival. NCI Drug Dictionary

Treatments listed in the registry

• Pembrolizumab (Biological): Pembrolizumab will be delivered via IV at 200mg on day 1 of each 3-week cycle for approximately 12 months. Cycle 1 begins 21 days prior to radiation therapy and cycles 2-17 are administered during and after radiation therapy.
• Olaparib (Drug): 200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.
• Androgen Deprivation Therapy (Drug): Androgen Deprivation Therapy (either LHRH agonist or LHRH antagonist) as per treating physician choice will be allowed within 3 months prior to randomization. Duration is per institutional standards.
• Radiation Therapy (Radiation): Definitive radiation (total dose and fractions) will be dosed per institutional standards. Definitive radiation may include external beam radiation therapy with or without brachytherapy, based on NCCN risk score and as per treating physicians.

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• radiation: Part of the study plan

Main goals

• Clinical Response Rate (6 months)

Other goals

• Biochemical-Free Survival
• Metastasis-Free Survival
• Time to Normalization of Serum Testosterone
• Molecular Alterations in Homologous Recombination Repair Genes

Planned enrollment: 64 (estimated).

• University of Kentucky, Lexington, Kentucky

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05568550
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C71721

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 13, 2026. Public record; not medical advice.