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 scintigraphy 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% and an absolute increase of ≥ 5 mm 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 lesions(s) by bone scintigraphy (as per the 2+2 PCWG3 criteria).
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 androgen receptor pathway inhibitor (androgen receptor pathway inhibitor \[ARPI\], enzalutamide, abiraterone, apalutamide, darolutamide).
Prior treatment with only one taxane therapy in the mCRPC setting. 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.
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History of central nervous system metastasis. Note: Participants with treated, asymptomatic, and clinically stable dural metastases are eligible.
History of allergic reactions or acute hypersensitivity reactions to the components of the trial therapies and their analogs. Participants with known contraindications to high-dose corticosteroids are also excluded.
History of malignancy that is expected to alter life expectancy or may interfere with disease assessments. Participants with prior history of malignancy that have been adequately treated and who have been disease-free for \>3 years are eligible, as are participants with adequately treated non-melanoma skin cancer or superficial bladder cancer.
Active autoimmune disease that has required systemic treatment (except physiologic replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on trial.
Known positive test for human immunodeficiency virus.
Presence or history of viral hepatitis infection.
Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of trial treatment with the following exceptions:
* Androgen-deprivation therapy with luteinizing hormone-releasing hormone/gonadotropin-releasing hormone (LHRH/GnRH) analogue (agonist/antagonist) is allowed.
* ARPIs (enzalutamide, abiraterone, apalutamide, darolutamide) require a minimum washout of 2 weeks prior to the first dose of xaluritamig.
* Prior prostate-specific membrane antigen (PSMA) radionuclide therapy cannot be given within 3 months prior to first dose of xaluritamig unless participant received \<2 cycles of therapy, in which case participant cannot have received PSMA radionuclide therapy within 35 days prior to first dose.
Any prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.
Any prior cluster of differentiation 3 (CD3)-directed therapy.
Requirement for chronic systemic corticosteroid therapy (prednisone dose \>10 mg/day or equivalent) or any other immunosuppressive therapies (including anti TNFα therapies).
Participation on any other xaluritamig trial, regardless of whether xaluritamig was administered.
