Background: ADT is associated with adverse events and decreased quality of life in pts with advanced PC. This study evaluates if APA + intermittent ADT in mCSPC pts who achieved prostate-specific antigen (PSA) <0.2 ng/mL after 6 mo of initial therapy with APA + ADT provides noninferior radiographic progression-free survival (rPFS) and reduces hot flash burden compared with APA + continuous ADT. Broad eligibility criteria, used to achieve greater inclusiveness of underserved populations, allow for increased diversity in race, ethnicity, gender identity, and physical disability of study pts. LIBERTAS is the first phase 3 study evaluating APA + intermittent vs continuous ADT in mCSPC pts. Methods: This prospective international, open-label, randomized study is enrolling pts with mCSPC, inclusive of all gender identities. Eligibility criteria: metastatic PC documented by conventional imaging (CT, MRI, or bone scan), ≤3 mo ADT prior to enrollment with the exception of pts receiving ADT as part of their gender-affirming care, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1; pts with ECOG PS 2 or 3 are eligible if their score is related to stable physical disabilities (eg, spinal cord injury or blindness) and not to PC or associated therapy. LIBERTAS is a de-gendered and trans-inclusive protocol seeking to drive recruitment and enrollment of pts in sexual and gender minority populations that are underserved and under-represented in clinical trials. Pts will receive APA 240 mg/d + ADT (GnRH agonist or antagonist) during the initial 6-mo treatment phase. Stratification: tumor volume and prior treatment for localized PC. Pts with confirmed PSA <0.2 ng/mL at the end of the initial 6-mo treatment phase will enter the main treatment phase and be randomized 1:1 to APA (240 mg/d) + intermittent ADT or APA + continuous ADT. ADT can be restarted in the APA + intermittent ADT group for pts with new/worsening cancer symptoms, PSA increase to >10 ng/mL (or return to baseline level when PSA was <10 ng/mL before start of ADT), or PSA doubling time <6 mo. Radiographic progression is assessed using conventional imaging. Primary end points are rPFS, measured by 18-mo event-free survival (EFS) rate, and reduction of hot flash burden measured by the hot flash severity adjusted score. Secondary end points include findings from objective digital health tools measuring sleep, activity and neurocognitive function, and patient-reported outcomes, including physical and mental wellbeing. ~333 pts will be enrolled over 2 yrs at 59 sites in 9 countries. An independent data monitoring committee will conduct an interim analysis for futility for the primary end point of 18-mo EFS rate and periodic review of safety data. Clinical trial information: NCT05884398.