Pembro With Radiation With or Without Olaparib

NCT ID: NCT05568550

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-27
• Study Completion Date: 2029-07-02

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.

Detailed Description

Immunotherapy and PARP-inhibitor are known to have radio-sensitizing effects when combined with radiation therapy. In addition, the combination with PARP-inhibitor and radiation can increase neoantigen expression, cytotoxic lymphocyte infiltration within the tumor microenvironment and increased immune stimulating cytokine concentration. Thus, there is a potential synergy of combining immunotherapy and PARP-inhibitor.

This is a phase 2 randomized 1:1 study. Subjects will be randomized to one arm (pembro + PARPi + standard of care therapy which is definitive radiation therapy combined with hormonal therapy) vs. another arm (pembro + standard of care therapy). All subjects will receive adjuvant immunotherapy for one year once they are done with definitive radiation treatment.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 - Pembrolizumab and Olaparib

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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 2 - Pembrolizumab

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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.

Androgen Deprivation Therapy

Intervention Type: 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

Intervention Type: 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.

Interventions

Pembrolizumab

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.

Intervention Type: BIOLOGICAL

Olaparib

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

Intervention Type: DRUG

Androgen Deprivation Therapy

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.

Intervention Type: DRUG

Radiation Therapy

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.

Intervention Type: RADIATION

Other Intervention Names

Keytruda; Lynparza

Eligibility Criteria

Inclusion Criteria

• 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
• Prior 5-alpha reductase inhibitor (for example, finasteride) for prostatic hypertrophy is allowed if discontinued at least 60 days prior to 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.

Exclusion Criteria

• PSA > 150ng/ml
• 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. Previous pelvic RT or major surgery (colorectal anastomosis, total cystectomy, radical prostatectomy, TURP, 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Zin W Myint

OTHER

Sponsor Role: lead

Responsible Party

Zin W Myint

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zin W Myint, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Kentucky

Lexington, Kentucky, United States

Site Status: RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Bryan Courtney

Role: CONTACT

bryancourtney@uky.edu

859-257-3379

Facility Contacts

Yvonne Taul, RN,CCRC

Role: primary

yvonne.taul@uky.edu

859-323-2354

Zin Myint, MD

Role: backup

zin.myint@uky.edu

410236809

Benjamin Maughan, MD, PharmD

Role: primary

benjamin.maughan@hci.utah.edu

801-581-2267

Other Identifiers

MCC-22-GU-80

Identifier Type: -

Identifier Source: org_study_id