TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Exclusion Criteria

• •Note: Participants are required to stop their prior ARPI after providing their consent to join this study. Participants with ongoing ARPI are eligible for a switch from their ongoing ARPI therapy if they have not progressed to CRPC disease, and meet any of the criteria, indicative of suboptimal biochemical response, or intolerability, as assessed by the Investigator.
• •Other permitted prior local therapy for mHSPC:
• •* Phase I and II: Prior prostate-directed radiation or surgical intervention. Radiation must be completed before study entry; surgery at least 2 weeks prior.
• •Participants with evidence of mCRPC or biochemical recurrence / PSA only disease or asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy and with normal PSA for ≥ 1 year prior to the start of study treatment.
• •Participants with PSA levels of ≤ 0.2 ng/mL at the start of study treatment.
• •Participants with CNS metastases are excluded unless:
• •* they have received prior therapy (e.g. surgery, radiotherapy, gamma knife), are neurologically stable and asymptomatic
• •* they are not receiving corticosteroid for the purpose of maintaining neurologic integrity and have baseline and subsequent radiological imaging of the brain.
• •* Participants with epidural disease, canal disease, or prior spinal cord involvement are excluded unless these areas have been treated, are stable, and the participant is not neurologically impaired.
• •Concurrent use of first-generation anti-androgens (like bicalutamide). Prior use of a first-generation anti-androgen drug in the context of ADT initiation with a GNRH analog is allowed, provided it was administered for ≤14 days and the last dose was administered ≥7 days from the study entry.
• •Systemic ketoconazole is used as antineoplastic treatment for prostate cancer.
• •Previous exposure to radioligand therapy.
• •Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
• •Previous treatment with any Polycomb Repressive Complex 2 (PRC2) inhibitor, including but not limited to Enhancer of Zeste Homolog 2 (EZH2) inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
• •Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study
• •Participants taking prohibited medication(s) (e.g., strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors that cannot be stopped within 7 days or 5 half-lives (whichever is longer) prior to study treatment and for the duration of the study treatment or prohibited herbal product(s) that cannot be stopped 7 days prior to study treatment.