The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypothesis is that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to radiographic progression free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as assessed by Blinded Independent Central Review (BICR), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.
Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening
Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI)
Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer [mHSPC] or non-metastatic hormone-sensitive prostate cancer [nmHSPC]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer [mCRPC] or non-metastatic castration-resistant prostate cancer [nmCRPC]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
Has presence of gastrointestinal condition
Is unable to swallow capsules/tablets
Has history of pituitary dysfunction
Has poorly controlled diabetes mellitus
Parallel
Opevesostat
DrugAdministered orally
Dexamethasone
DrugAdministered orally
Fludrocortisone acetate
DrugAdministered orally
Hydrocortisone
DrugAdministered orally or IM as a rescue drug
Abiraterone acetate
DrugAdministered orally
Prednisone acetate
DrugAdministered orally
Enzalutamide
DrugAdministered orally
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time to Initiation of the First Subsequent Anticancer Therapy (TFST)
TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurred first.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Duration of Response (DOR)
For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death from any cause, whichever occurs first.
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