SUMMARY

• PROTEUS (NCT03767244) is an ongoing phase 3, randomized, double-blind, placebocontrolled, multicenter study evaluating the efficacy and safety of ERLEADA plus androgen deprivation therapy (ADT) compared to placebo plus ADT before and after radical prostatectomy (RP) in patients with localized or locally advanced high-risk prostate cancer. The dual primary endpoints are pathologic complete response (pCR) rate and metastasis-free survival (MFS). The study is expected to enroll approximately 2000 patients from >203 sites in 18 countries. Safety and efficacy results from the PROTEUS study have not been published.^1,2

CLINICAL DATA

PROTEUS Study

PROTEUS is an ongoing study evaluating the safety and efficacy of ERLEADA plus ADT compared to placebo plus ADT before and after RP in patients with localized or locally advanced high-risk prostate cancer.^1,2

Study Design/Methods

• Phase 3, randomized, double-blind, placebo-controlled, multicenter study
• Approximately 2000 patients from >203 sites in 18 countries will be randomized 1:1 to receive the following treatments for 6 months prior to RP (cycles 1-6) and for 6 months following RP (cycles 7-12):
  • ERLEADA 240 mg orally once daily plus ADT
  • Placebo plus ADT
• All patients will receive ADT to maintain castrate concentrations of testosterone (<50 ng/dL).
• Conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) and bone scan will be conducted at baseline, within 4 weeks after RP, at biochemical failure (BCF; defined as 2 consecutive prostate-specific antigen [PSA] rises with the second consecutive test resulting in an absolute PSA value of ≥0.2 ng/mL), and then every 6 months following BCF until distant metastasis is documented by blinded independent central review (BICR) or death.
• Patients will undergo cardiovascular and thrombotic risk assessment at screening, prior to RP, and after RP.
• PSA testing and radiological assessment for progression is permitted in the neoadjuvant setting (cycles 1-6).
• Adjuvant or salvage radiation therapy (RT) post RP may be performed at the discretion of the investigator (cycles 7-12).
• Following treatment, PSA levels will be monitored every 3 months for BCF. Prostatespecific membrane antigen positron emission tomography (PSMA-PET) imaging will be conducted 3 months after end of adjuvant treatment, at BCF, and then every 6 months following BCF until distant metastasis or death.
• Patients will be stratified by pelvic node status (N0 or N1), Gleason score (GS) (7 or ≥8), and region (North America, Europe, or the rest of the world).
• Select inclusion criteria: histologically confirmed high-risk prostate adenocarcinoma based on GS and Gleason Grade Group criteria; candidate for RP with lymph node dissection per investigator; Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1; ability to receive ADT for at least 13 months per cardiovascular risk and investigator’s assessment
• Select exclusion criteria: active malignancies which required treatment in the last 24 months (exceptions include cured skin cancer, low-risk non-muscle-invasive urothelial cancer, and breast cancer [adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence]); distant metastasis (M1), M0 on conventional imaging confirmed by central radiology review, nodal disease below the iliac bifurcation allowed; prior treatment with antiandrogen or treatment with ADT prior to signing study informed consent form; bilateral orchiectomy; history of pelvic radiation for prostate cancer; history of seizure or condition that may predispose to a seizure; treatment with drugs known to lower the seizure threshold ≤4 weeks prior to randomization; treatment with any investigational agent ≤4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time; cardiovascular events ≤12 months prior to first dose of study drug
• Dual primary endpoints: pCR rate and MFS (assessed by BICR)
• Secondary endpoints: PSA-free survival and progression-free survival (PFS)
• Additional endpoints: time to castration-resistant prostate cancer; overall survival; second PFS; time to BCF; time to testosterone recovery; percentage of patients with no evidence of disease on PSMA-PET imaging; percentage of patients receiving postoperative RT; time to first subsequent therapy (including re-initiation of ADT); patient-reported outcomes; MFS based on PSMA-PET or conventional imaging; failurefree survival
• The total time to final analysis is estimated to be 7.5 years (3 years accrual and 4.5 years follow-up).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 25 February 2024.