A Study of Xaluritamig Plus Abiraterone Versus Investigator's Choice in Participants With Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

Amgen

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Xaluritamig; Drug: Docetaxel; Drug: Cabazitaxel; Drug: Abiraterone acetate

Study type: Interventional

Funder types: Industry

Identifiers

NCT07213674

20230239

Details and patient eligibility

About

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).

Enrollment: 750 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

750 participants in 2 patient groups

Xaluritamig Plus Abiraterone

Experimental group

Description:

Participants will be randomized to receive xaluritamig in combination with abiraterone acetate.

Treatment:

Drug: Abiraterone acetate

Drug: Xaluritamig

Investigator's Choice

Active Comparator group

Description:

Participants will receive investigator's choice of: * Abiraterone acetate orally, once daily or * Docetaxel IV Q3W or * Cabazitaxel IV Q3W.

Treatment:

Drug: Abiraterone acetate

Drug: Cabazitaxel

Drug: Docetaxel