Pembrolizumab plus intensive androgen-blocking before prostatectomy for high-risk localized prostate cancer

Phase II Study of Neoadjuvant Pembrolizumab Plus Intensive Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer

Phase 2 Interventional Portland VA Medical Center · NCT03753243

This trial tests whether giving pembrolizumab together with intensive androgen-blocking (enzalutamide) before prostatectomy helps men with high-risk localized prostate cancer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment32 (estimated)
Ages18 Years and up
SexMale
SponsorPortland VA Medical Center Federal
Drugs / interventionsPembrolizumab
Locations1 site (Portland, Oregon)
Trial IDNCT03753243 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase II trial gives pembrolizumab and enzalutamide before prostatectomy with extended pelvic lymph node dissection in men with high-risk localized prostate cancer. Participants receive pembrolizumab 200 mg IV every 3 weeks and enzalutamide 160 mg orally daily for a neoadjuvant period prior to radical prostatectomy. The primary endpoint is pathologic complete response (no detectable cancer in the prostatectomy specimen), and safety and clinical outcomes are also recorded. Eligible patients are adults with non-metastatic prostate adenocarcinoma who meet at least one high-risk criterion (Gleason ≥8, PSA >20 ng/mL, or clinical T3a) and have ECOG performance status 0–1.

Who should consider this trial

Good fit: Men with non-metastatic high-risk prostate adenocarcinoma planning prostatectomy, ECOG 0–1, life expectancy ≥10 years, and at least one high-risk feature (Gleason ≥8, PSA >20, or clinical T3a).

Not a fit: Patients with metastatic disease, lower-risk prostate cancer, poor performance status, or contraindications to immunotherapy or androgen-axis blockade are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could increase complete tumor eradication at surgery and lower the chance of recurrence.

How similar studies have performed: PD-1 inhibitors alone have shown limited activity in prostate cancer, and neoadjuvant combinations with AR-targeted therapy are investigational with some early signals but no consistent pCR benefits to date.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Be willing and able to provide written informed consent/assent for the trial.
* Capability to understand and comply with the protocol and signed informed consent document.
* Be ≥ 18 years of age on day of signing informed consent.
* Have measurable disease based on RECIST 1.1.
* Histologically confirmed, non-metastatic adenocarcinoma of the prostate
* Prostatectomy with extended lymph node dissection planned as primary therapy
* 10 year or longer life expectancy based on other co-morbidities
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* Any one of the following three high risk features:

  * Gleason grade \> 8-10
  * PSA \> 20 ng/ml
  * Clinical stage T3a (resectable)
* No evidence of metastases .
* No other diagnosis of malignancy (with exception of non-melanoma skin cancer or a malignancy diagnosed ≥5 years ago).
* Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through the time of surgery. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Demonstrate adequate organ function, all screening labs should be performed within 30 days of treatment initiation.

Where this trial is running

Portland, Oregon

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Prostate CancerNeoadjuvantProgrammed cell death protein 1
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.