LIBERTAS: A Degendered and Transgender-Inclusive Phase 3 Study of Apalutamide (APA) Plus Intermittent Vs Continuous Androgen Deprivation Therapy (ADT) in Participants (pts) with Metastatic Hormone-Sensitive Prostate Cancer (Mhspc).

TPS5119 Background: Individuals with mHSPC may experience adverse events and decreased quality of life associated with ADT. LIBERTAS, the first degendered and transgender-inclusive PC study, explores the use of APA + intermittent ADT as an ADT-minimizing approach in pts who achieve prostate-specific antigen (PSA) <0.2 ng/mL after 6 mo of APA + ADT. mHSPC has been studied almost exclusively in cisgender men. With inclusion of transgender pts who may be receiving feminizing gender-affirming care (GAC), reducing ADT must be approached with deliberate care. LIBERTAS uses broad eligibility criteria to allow inclusion of pts under-represented in clinical trials, including Black and African American pts, transgender, nonbinary, and gender-diverse pts and pts with disabilities. Methods: A patient voice exercise was conducted to gather feedback from pts and caregivers on their experiences with mHSPC and on the proposed study design. All gender-specific language was removed. SOGI (sexual orientation and gender identity) data are collected and reported in the United States. Study site staff are offered healthcare-specific sexual and gender minority cultural sensitivity training. This prospective, international, open-label, randomized study is enrolling pts with metastatic PC documented by conventional imaging, ≤3 mo ADT before enrollment (except as part of GAC), and ECOG PS 0/1; pts with ECOG PS 2/3 are eligible if their score is related to stable disabilities (eg, spinal cord injury, blindness) and not to PC/PC therapy. Pts with bilateral orchiectomy are excluded (except as part of GAC). Stratification factors: tumor volume and prior treatment for localized PC. Pts with confirmed PSA <0.2 ng/mL after initial 6-mo treatment with APA 240 mg/d + ADT are randomized 1:1 to APA 240 mg/d + intermittent ADT or APA + continuous ADT. ADT can be restarted until radiographic progression (assessed by conventional imaging) for pts in the intermittent ADT group with new/worsening cancer symptoms, PSA increase to >10 ng/mL (or return to baseline when PSA <10 ng/mL before ADT), or PSA doubling time <6 mo. Outcomes of pts undergoing medical or surgical GAC are evaluated descriptively as a separate cohort. Primary end points: radiographic progression-free survival and hot flash frequency and severity score at 18 mo from randomization. Secondary end points include findings from electronic patient-reported outcomes completed on a mobile device, digital health assessments measuring physical activity and sleep (measured from a wrist-worn device), and neurocognitive function measured using touchscreen-based interactive assays. An independent data monitoring committee will review safety data. ~333 pts will be enrolled over 2 yrs at 86 sites in 9 countries. Clinical trial information: NCT05884398 .