The primary objective of this study is to compare overall survival (OS) in participants receiving xaluritamig plus abiraterone against investigator's choice (docetaxel, cabazitaxel, or abiraterone).

Inclusion Criteria:

• Participant has provided informed consent before 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.

• Metastatic castration-resistant prostate cancer (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 before enrollment.

• Evidence of progressive disease (PD), defined as 1 or more PCWG3-modified RECIST 1.1 criteria:

  • Serum PSA progression is defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimum 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 1 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 scan (as per the 2+2 PCWG3-modified RECIST 1.1 criteria).

• Participants must have had prior orchiectomy and/or ongoing androgen-deprivation therapy (ADT) and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).

• Prior disease progression on 1, and only 1, androgen receptor pathway inhibitor (ARPI) (either enzalutamide, apalutamide, or darolutamide) is required.

• Participants intended to receive cabazitaxel must have previously received ≤ 6 cycles of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

• Adequate organ function.

Exclusion Criteria:

Disease Related:

• Participants with a history of central nervous system (CNS) metastases.
• Unresolved toxicities from prior antitumor therapy not having resolved to CTCAE version 5.0 grade 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.

Prior/Concomitant Therapy:

• Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.

• Prior disease progression on or intolerance to abiraterone.

• Prior treatment with any chemotherapy regimen in the mCRPC setting and/or > 6 cycles of docetaxel treatment in the mHSPC setting.

• Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks before first dose of study treatment with the following exceptions:

  • Androgen receptor pathway inhibitors (ARPIs; enzalutamide, darolutamide, apalutamide): minimum washout of 2 weeks prior to the first dose of study treatment.
  • Androgen suppression therapy (eg, luteinizing hormone-releasing hormone/gonadotrophin releasing hormone [LHRH/GnRH] analogue [agonist/antagonist]) is permitted.

• Prior radioligand therapy (RLT) within 8 weeks of first dose of study treatment.

• Prior radionuclide therapy (radium-223) within 2 months of first dose of study treatment.

• Prior palliative radiotherapy within 2 weeks before first dose of study treatment. Participants must have recovered from all radiation-related toxicities.

• Concurrent cytotoxic chemotherapy, ARPI, immunotherapy, RLT, poly adenosine diphosphate ribose polymerase (PARP) inhibitor, biological therapy, investigational therapy.

• Treatment with live and live-attenuated vaccines within 4 weeks before the first dose of study treatment.

• Prior CD3-directed therapy.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.