SUMMARY  

• PRIMORDIUM (NCT04557059) is an ongoing, phase 3, randomized, open-label, multicenter study evaluating the efficacy and safety of adding ERLEADA to radiotherapy and a luteinizing hormone-releasing hormone agonist (LHRHa) compared to radiotherapy and a LHRHa alone in patients with high-risk, prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-positive hormone-sensitive prostate cancer (HSPC). The primary endpoint is PSMA-PET metastatic progression-free survival (ppMPFS). This study also includes an observational cohort of PSMA-PET-negative patients. Efficacy and safety results have not been published. Baseline characteristics of patients enrolled in both cohorts through the data cutoff date January 12, 2023 have been published.^1-3

CLINICAL DATA

PRIMORDIUM Study

PRIMORDIUM is an ongoing, phase 3, randomized, open-label, multicenter, global study evaluating the efficacy and safety of adding ERLEADA to radiotherapy and a LHRHa compared to radiotherapy and a LHRHa alone in high-risk patients with PSMA-PET-positive HSPC. Patients who are PSMA-PET-negative at baseline will be enrolled into the observational cohort.^1-3

Study Design/Methods

• A total of ~412 PSMA-PET-positive patients to achieve ~192 events and ~200 PSMA-PET-negative patients will be included in the interventional and observational cohorts, respectively. This study is not designed to compare results across cohorts.
• The treatments in the interventional cohort are randomized 1:1 as described in the Table: Treatments in the Interventional Cohort.
• Patients who are PSMA-PET-negative and enrolled in the observational cohort will receive standard-of-care (SOC) treatment per local practice and will have data collected during routine clinical practice which will include therapies administered, clinical evaluations, disease progression assessments, and survival until closure of the interventional cohort.

• Patients in the interventional cohort will be stratified by location of PSMA-PET-positive lesions, prostate-specific antigen (PSA) doubling-time (PSADT), and planned use of stereotactic body radiotherapy (SBRT).
  • At sites where it is a standard approach, SBRT may be used for ≤3 PSMA-avid distant metastases; the decision to use SBRT must be made before randomization.
• In the interventional cohort, PSA will be measured every 3 months until the primary endpoint. If the PSA remains <0.2 ng/mL, PSMA-PET is assessed by blinded independent central review (BICR) at 6 and 12 months, then annually until PSMA-PET progression. If PSA rises to ≥0.2 ng/mL, PSMA-PET is done immediately then every 6 months until PSMA-PET progression. Testosterone and patient-reported outcomes (PROs) will additionally be assessed.
  • Post-PSMA-PET-progression assessments will include bone scans, computed tomography (CT)/magnetic resonance imaging (MRIs), and PROs.
• Select inclusion criteria: histologically confirmed adenocarcinoma of the prostate; previously treated with radical prostatectomy (RP) with or without lymph node dissection and either any post-operative PSA of <0.1 ng/mL within 12 months after RP and without any PSA ≥0.1 ng/mL within the 4 to 8-week period after RP for biochemical recurrence after RP or PSA ≥0.1 ng/mL within the 4 to 8-week period after RP for persistent PSA after RP, confirmed by additional measurement at least 3 weeks later; biochemically recurrent prostate cancer after RP with high risk of developing metastasis defined as pathological Gleason score ≥8 or PSADT ≤12 months; no evidence of metastases on screening CT/MRI of the chest/abdomen/pelvis, and technetium-99m (^99mTc) whole-body bone scan; Eastern Cooperative Oncology Group performance status (ECOG PS) grade 0 or 1; results of PSMA-PET at screening as determined by BICR had to be:
  • PSMA-PET-negative for any prostate cancer lesions (ie, no locoregional lesion and no distant lesions)
  • PSMA-PET-positive for ≥1 locoregional (pelvic) lesion without distant extra pelvic lesion
  • PSMA-PET-positive for ≥1 locoregional (pelvic) lesion with extra pelvic lesion(s)
• Select exclusion criteria: history of pelvic radiation for malignancy; history of ADT or chemotherapy for prostate cancer; prior treatment for biochemical recurrence; prior treatment with a CYP17 inhibitor, androgen receptor (AR) antagonist, medication that lowers androgen levels, or bilateral orchiectomy; small cell or neuroendocrine carcinoma of the prostate; clinically significant cardiovascular disease; use of 5-alpha-reductase inhibitor or an investigational agent ≤4 weeks prior to randomization; history of seizure or at increased risk of seizure  
• Primary endpoint: ppMPFS, defined as the appearance of at least 1 new PSMA-PET-positive distant lesion compared with the previous scan assessed by BICR, or death
• Secondary endpoints: time to PSA progression; PSA response rate; PSA levels at end of week 26; time to locoregional progression by PSMA-PET; overall survival (OS); prostate cancer-specific survival; and adverse events

Results

Baseline Characteristics

• Baseline characteristics of patients enrolled in both cohorts through the data cutoff date January 12, 2023 are reported in Table: Baseline Characteristics of Interventional and Observational Cohorts.
• By the data cutoff date, enrolled patients were from Australia, Austria, Belgium, Brazil, Czech Republic, Denmark, Hungary, Italy, Lebanon, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, and Turkey in both cohorts, with the exception of Hungary (observational cohort only) and Lebanon (interventional cohort only). As of December 31, 2023, the United States is among the countries added with active sites.

Efficacy and safety results have not been published.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 05 February 2025.