A Study of Mevrometostat With Enzalutamide in People With Prostate Cancer Who Have Previously Received Androgen Receptor Pathway Inhibitor Therapy

Inclusion Criteria:

* Willing and able to provide written informed consent
* Age 18 years or older
* Diagnosis of prostate cancer (adenocarcinoma) confirmed by tissue sample, without neuroendocrine or small cell features
* Currently taking or recently treated with enzalutamide, darolutamide, or apalutamide (within 30 days of screening) and willing to switch to or restart enzalutamide for this study
* Cancer has spread to bone or soft tissue (metastatic disease), confirmed by imaging
* ECOG performance status of 0, 1, or 2 (able to care for self and up and about more than 50% of waking hours)
* Testosterone level less than 50 ng/dL at screening, with ongoing hormone deprivation therapy or prior surgical castration
* If receiving bone-protective therapy (e.g., denosumab or bisphosphonates), must be on a stable dose for at least 4 weeks
* Evidence of cancer progression while on enzalutamide, darolutamide, or apalutamide, shown by rising PSA, worsening disease on imaging, or new bone lesions
* Adequate organ function based on blood tests within 28 days of starting treatment, including adequate blood counts, kidney function, and liver function
* Willing to use acceptable birth control during the study and for 30 days after the last dose

Exclusion Criteria:

* History of myelodysplastic syndrome, acute myeloid leukemia, or other prior cancer (exceptions: non-melanoma skin cancer, carcinoma in situ, cancers more than 3 years ago with no recurrence, or early-stage cancers with low risk of recurrence)
* Any medical or psychiatric condition, including active infection or recent suicidal ideation, that may make study participation unsafe
* History of seizure or conditions that may increase seizure risk (e.g., prior stroke, significant brain trauma), or loss of consciousness or transient ischemic attack within 12 months
* Untreated brain metastases, spinal cord compression, or clinically significant epidural disease
* Use of 5-alpha reductase inhibitors, herbal medications, or supplements known to alter PSA levels within 4 weeks of starting treatment
* AIDS-related illness or active hepatitis B or C (well-controlled HIV is allowed)
* Known history of chronic liver disease (e.g., alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, Wilson's disease, hemochromatosis)
* Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or prior gastric resection or lap-band surgery
* Clinically significant cardiovascular disease within the past 6 months (e.g., heart attack, unstable angina, stroke, heart failure NYHA Class III/IV, pulmonary embolism, significant arrhythmias), cardiac pacemaker, or QTcF greater than 480 msec on screening ECG
* Prior or current use of PARP inhibitors and/or AKT inhibitors
* Prior cancer progression on abiraterone (stopping abiraterone due to side effects is allowed)
* Known allergy to any study drug
* Blood transfusion within 28 days prior to screening blood tests
* Use of another investigational drug within 4 weeks before starting study treatment
* Any other condition that, in the opinion of the investigator, would prevent safe participation
* Current use or anticipated need for strong CYP3A4/5 inhibitors or inducers (other than enzalutamide) within 10 days or 5 half-lives prior to treatment start