Pembro With Radiation With or Without Olaparib

NCT05568550 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-22-GU-80
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will evaluate whether the immune-sensitizing effects of immunotherapy (Pembrolizumab) and radiation with or without a PARP-inhibitor (Olaparib) will increase the effects of immunotherapy in men with high-risk localized prostate cancer.

Conditions

Prostate Cancer

Keywords

immunotherapy; PARP; radiation; androgen deprivation therapy; ADT; PD-1

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rate

  The proportion of patients who achieve a PSA nadir level of ≤ 0.06ng/mL six months after completion of radiation therapy.

  6 months

Secondary Outcomes (4)

• Biochemical-Free Survival

  3 years

• Metastasis-Free Survival

  3 years

• Time to Normalization of Serum Testosterone

  3 years

• Molecular Alterations in Homologous Recombination Repair Genes

  3 years

Other Outcomes (5)

• PSA Progression-Free Survival

  3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)

• Correlation between clinical outcome and immune cell subtype.

  3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)

• Correlation between clinical outcome and cytokine levels.

  3 years (Pre-treatment baseline, cycle 3, 6 months or at disease progression)

Study Arms (2)

Arm 1 - Pembrolizumab and Olaparib

EXPERIMENTAL

Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.

Biological: Pembrolizumab; Drug: Olaparib; Drug: Androgen Deprivation Therapy; Radiation: Radiation Therapy

Arm 2 - Pembrolizumab

EXPERIMENTAL

Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.

Biological: Pembrolizumab; Drug: Androgen Deprivation Therapy; Radiation: Radiation Therapy

Interventions

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.

Also known as: Keytruda

Arm 1 - Pembrolizumab and Olaparib; Arm 2 - Pembrolizumab

Olaparib DRUG

200mg Olaparib will be given twice daily for a total of 3 cycles. Cycle 1 begins 21-days prior to radiation therapy.

Also known as: Lynparza

Arm 1 - Pembrolizumab and Olaparib

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.

Arm 1 - Pembrolizumab and Olaparib; Arm 2 - Pembrolizumab

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.

Arm 1 - Pembrolizumab and Olaparib; Arm 2 - Pembrolizumab

Eligibility Criteria

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

You may qualify 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 may not qualify 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

Sponsors & Collaborators

• Zin W Myint: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab; olaparib; Androgen Antagonists; Radiotherapy

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)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics

Study Officials

• Zin W Myint, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bryan Courtney

CONTACT

859-257-3379; bryancourtney@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 1:1

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 5, 2022
• Study Start: July 27, 2023
• Primary Completion (Estimated): July 2, 2026
• Study Completion (Estimated): July 2, 2029
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)