Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer

Amgen

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Cabazitaxel; Drug: Enzalutamide; Drug: Abiraterone; Drug: Xaluritamig

Study type: Interventional

Funder types: Industry

Identifiers

NCT06691984

2024-513968-25 (Other Identifier)

20230005

Details and patient eligibility

About

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]).

Enrollment: 675 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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675 participants in 2 patient groups

Xaluritamig

Experimental group

Description:

Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.

Treatment:

Drug: Xaluritamig

Cabazitaxel/Abiraterone/Enzalutamide

Active Comparator group

Description:

Participants with mCRPC will be randomized to receive cabazitaxel as an IV infusion, or a second androgen receptor-directed therapy of either abiraterone as oral tablets, or enzalutamide as oral tablets at the investigator's discretion.

Treatment:

Drug: Enzalutamide

Drug: Abiraterone

Drug: Cabazitaxel