Overview
The main objective of the study is to compare overall survival in participants receiving xaluritamig versus investigator's choice (cabazitaxel or second androgen receptor-directed therapy [ARDT]).
Eligibility
Inclusion Criteria:
- 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.
- 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.
- Progression of bone disease: evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria, Scher et al, 2016).
- 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 treatment with at least one ARDT.
- Prior treatment with one taxane therapy. Prior treatment with docetaxel in the hormone-sensitive setting is permitted. Participants who received two or more prior chemotherapy regimens in the castrate-resistant setting are not eligible.
- Prior treatment with radioligand therapy (RLT), radionuclide therapy (Radium-223), poly ADP-ribose polymerase (PARP) inhibitor, or immune checkpoint inhibitor is permitted.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- Adequate organ function.
Key Exclusion Criteria:
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.
- Prior Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT) within 2 months of the first dose of study treatment unless participants received < 2 cycles of therapy. Participants who received 1 cycle of PSMA RLT within 35 days prior to the first dose of study treatment are also excluded.
- Participants who started a bisphosphonate or denosumab regimen within 4 weeks prior to the first dose of study treatment.
- Radiation therapy within 4 weeks prior to the first dose of study treatment (or local or focal radiotherapy within 2 weeks prior to the first dose of study treatment).
- Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.
Disease Related:
- Participants with a history of central nervous system (CNS) metastasis.
- Unresolved toxicities from prior anti-tumor therapy with 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.