Pembro With Radiation With or Without Olaparib

Phase 2

Recruiting

• Conditions: Prostate Cancer
• Interventions: Biological: Pembrolizumab; Drug: Androgen Deprivation Therapy; Drug: Olaparib; Radiation: Radiation Therapy

• Registration Number: NCT05568550
• Lead Sponsor: Zin W Myint

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.

Study Timeline

• Study First Submitted: 2022-09-29
• Study First Submitted QC: 2022-10-03
• Study First Posted: 2022-10-05
• Study Start: 2023-07-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2026-07-02
• Study Completion: 2029-07-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2 - Pembrolizumab	Androgen Deprivation Therapy	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
Arm 2 - Pembrolizumab	Radiation Therapy	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.
Arm 1 - Pembrolizumab and Olaparib	Pembrolizumab	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Arm 1 - Pembrolizumab and Olaparib	Androgen Deprivation Therapy	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Arm 1 - Pembrolizumab and Olaparib	Radiation Therapy	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Arm 1 - Pembrolizumab and Olaparib	Olaparib	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab and Olaparib.
Arm 2 - Pembrolizumab	Pembrolizumab	Patients with high-risk prostate cancer receiving combination therapy with Pembrolizumab.

Primary Outcome Measures

Name	Time	Method
Clinical Response Rate	6 months	The proportion of patients who achieve a PSA nadir level of ≤ 0.06ng/mL six months after completion of radiation therapy.

Secondary Outcome Measures

Name	Time	Method
Biochemical-Free Survival	3 years	Biochemical-free survival rate at 3 years as defined by Phoenix Criteria.
Molecular Alterations in Homologous Recombination Repair Genes	3 years	Molecular alterations in the homologous recombination repair (HHR) genes.
Time to Normalization of Serum Testosterone	3 years	Time from normalization is the date of first return to normal serum testosterone 270 ng/ml or greater after withdrawal of androgen deprivation therapy.
Metastasis-Free Survival	3 years	Metastasis-free survival rate at 3 years as defined by RECIST v1.1 criteria.

Trial Locations

Locations (2)

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States