SUMMARY  

• LIBERTAS (NCT05884398) is an ongoing, phase 3, prospective, randomized, open-label, multicenter, global study evaluating the efficacy and safety of ERLEADA with intermittent vs continuous androgen deprivation therapy (ADT) following undetectable prostate-specific antigen (PSA) response (<0.2 ng/mL) in patients with newly-diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), inclusive of all gender identities. After 6 months of initial treatment with ERLEADA and ADT, patients with PSA response enter the main treatment phase and will be treated with either ERLEADA and intermittent ADT or ERLEADA and continuous ADT. The coprimary endpoints are radiographic progression-free survival (rPFS) and hot flash severity score and frequency at 18 months from randomization. Enrollment is planned for approximately 333 patients.^1-3 Efficacy and safety results have not been published.
  • As of May 9, 2024, 15 patients representing racial and ethnic minority backgrounds and 1 sexual and gender minority patient (self-identified as “Gay Man”) have been enrolled.²

CLINICAL DATA

LIBERTAS Study

LIBERTAS is an ongoing, phase 3, prospective, randomized, open-label, multicenter, global study evaluating the efficacy and safety of ERLEADA with intermittent vs continuous ADT following PSA response in patients with newly diagnosed mHSPC, inclusive of all gender identities.^1-3

Study Design/Methods

• Planned enrollment includes approximately 333 patients over 2 years at 86 sites across 9 countries.
• During the initial 6-month treatment phase, patients receive ERLEADA 240 mg/day orally and ADT, with the choice of ADT (gonadotropin-releasing hormone agonist or antagonist) per investigator discretion. Based on PSA response, patients were assigned as follows:
  • Undetectable PSA (<0.2 ng/mL): patients randomized 1:1 to Arm A (ERLEADA 240 mg/day orally with intermittent ADT) or Arm B (ERLEADA 240 mg/day orally with continuous ADT) in the main treatment phase.
  • Detectable PSA (≥0.2 ng/mL): patients continue standard of care off study.
• Patient recruitment and enrollment includes a degendered and transgender-inclusive protocol, as well as nonbinary and gender-diverse patients. Patients with an undetectable PSA response undergoing gender-affirming care will be evaluated as a separate cohort. These patients will not be randomized in the main treatment phase and will be treated continuously with ERLEADA from study initiation until disease progression.
• Patients in Arm A can restart ADT with new or worsening cancer symptoms, PSA increase to >10 ng/mL (or return to baseline level when PSA was <10 ng/mL before starting ADT) or PSA doubling time <6 months.
• The main treatment phase and follow-up is ~24 months after the last patient is randomized.
• Patients will be stratified by tumor volume and prior treatment for localized prostate cancer.
• Quality of life (QoL) assessments will be based on subjective patient-reported outcomes (PROs) and objective data from digital health tools (eg, measure of sleep, activity and neurocognitive functions) in both treatment arms.
• Select inclusion criteria: metastatic prostate cancer (≥2 distinct extraprostatic sites of metastasis) documented by conventional imaging (computed tomography [CT], magnetic resonance imaging [MRI], or bone scan) and/or next-generation imaging (e.g. prostate-specific membrane antigen positron emission tomography [PSMA PET] scan), inclusive of all gender identities; testosterone >50 ng/dL at screening (except those who received ADT prior to screening); ≤3 months of ADT prior to enrollment (except patients receiving ADT as part of their gender-affirming care); Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, however those with ECOG PS 2-3 are eligible if score is related to stable physical disabilities (eg, spinal cord injury, blindness) and not to prostate cancer or associated therapy.
• Select exclusion criteria: pelvic lymph nodes as only site of metastasis; prior treatment for metastatic prostate cancer; ≤3 months of ADT combined with focal radiation to an oligometastatic site; prior bilateral orchiectomy (except those who completed this procedure as gender-affirming care without progressive prostate cancer thereafter in order to be considered mHSPC); for localized or locally advanced prostate cancer, patients must have received ≤3 years total of ADT and all other forms of prior systemic therapies for prostate cancer and all such therapies completed ≥1 year prior to the first dose of ERLEADA (except those receiving gender-affirming hormonal therapy); surgical intervention for prostate cancer within 28 days of study drug initiation; history of seizure or known condition determined to significantly predispose to seizure per investigator; any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events.  
• Coprimary endpoints: rPFS at 18 months from randomization; hot flash severity score and hot flash frequency at 18 months from randomization.
  • Radiographic progression assessment will be via conventional imaging.
  • Hot flashes evaluations will be via the Hot Flash Related Daily Interference Scale PRO questionnaire.
• Key secondary endpoints: mean daily changes in hot flash severity score from baseline to all postrandomization visits; progression-free survival on subsequent therapy (PFS2); overall survival (OS) and cancer-specific survival; PSA outcomes; duration of time on ADT; duration of time with testosterone <50 ng/dL; time to recovery of testosterone >50 ng/dL; time to metastatic castration-resistant prostate cancer (mCRPC); safety; PROs, QoL, hot flash-related QoL; clinical (wearable) and neurocognitive insights.

Efficacy and safety results have not been published.

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
30 May 2024.