Mass General - Division of Clinical Research

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures. - Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent. - Participant must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted. - mCRPC with ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained within 28 days prior to enrollment. - Evidence of progressive disease, defined as 1 or more PCWG3 criteria: - Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. - Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions. - Progression of bone disease: defined by the appearance of at least 2 new bone lesion(s) by bone scan (as per the 2+2 PCWG3 criteria). - Participants must have had a prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L). - Prior progression on at least one ARDT (enzalutamide, abiraterone, apalutamide, darolutamide). - Prior treatment with only one taxane therapy in the mCRPC setting. Note: Prior treatment with docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting is permitted; however, participants must have also received one, and only one, taxane therapy in the mCRPC setting. - Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. - Adequate organ function.

Prior & Concomitant Therapy: - Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy. - Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks prior to the first dose of study treatment, not including androgen suppression therapy (eg, luteinizing hormone-releasing hormone/gonadotropin-releasing hormone [LHRH/GnRH] analogue [agonist/antagonist]). - Prior Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT) within 3 months of the first dose of study treatment unless participants received < 2 cycles of therapy. - Prior palliative radiotherapy within 2 weeks of first dose of study treatment. Participants must have recovered from all radiation-related toxicities. - Concurrent cytotoxic chemotherapy, ARDT, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, investigational therapy. Note: Prior treatment with a PARP inhibitor is permitted as long as not within 4 weeks before first dose of study treatment. - Prior radionuclide therapy (Radium-223) within 2 months of first dose of study treatment. - Treatment with live and live-attenuated vaccines within 4 weeks before the first dose of study treatment. Disease Related: - Participants with a history of central nervous system (CNS) metastasis. Note: Participants with treated, asymptomatic, and clinically stable dural metastases are eligible. - Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE version 5.0 events grade above 1 or baseline, with the exception of alopecia or toxicities that are stable and well controlled AND there is an agreement to allow inclusion by both the investigator and the sponsor.