Neoadjuvant Pembrolizumab Plus Androgen Axis Blockade Prior to 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

Pembrolizumab will be administered at a dose of 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Enzalutamide will be administered at dose of 160 mg orally every day. All patients will be required to have at least one high-risk criteria.

The investigators propose to study the effects of pembrolizumab combined with intensive androgen receptor (AR) targeting prior to prostatectomy with extended pelvic lymph node dissection in subjects with high-risk localized prostate cancer (HRLPC).

Trial Design- single arm, single-stage, open label Phase II of neoadjuvant immune-hormonal therapy in high-risk localized prostate cancer.

Objectives To evaluate efficacy and safety of pembrolizumab combined with intensive AR targeting prior to prostatectomy in subjects with high-risk localized prostate cancer (HRLPC).

Primary Endpoint Pathologic complete response (pCR) defined as absence of detectable malignant cells in the prostatectomy specimen evaluated by standard histologic techniques.

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.