Adding xaluritamig to androgen receptor pathway inhibitors for metastatic hormone-sensitive prostate cancer

A Phase 1b Open-label, Multicenter Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer

This trial tests whether adding xaluritamig to darolutamide or abiraterone is safe and tolerable for men with high-volume metastatic hormone-sensitive prostate cancer who have recently started hormone therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Amgen (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 14 sites (San Francisco, California and 13 other locations)
• Trial ID: NCT07140900 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial gives escalating doses of xaluritamig together with either darolutamide or abiraterone to determine safety and tolerability in men with de novo high-volume metastatic hormone-sensitive prostate cancer. Participants must have histologically confirmed prostate adenocarcinoma, have started androgen deprivation therapy within 12 weeks, and may not have received prior docetaxel. The study will closely monitor adverse events, laboratory values, and tolerability to identify a recommended dose for future testing. Treatment and follow-up are conducted at specialized U.S. cancer centers.

Who should consider this trial

Good fit: Ideal candidates are men with de novo high-volume metastatic hormone-sensitive prostate adenocarcinoma who began androgen deprivation therapy within the past 12 weeks and have not received prior docetaxel.

Not a fit: Patients with non-adenocarcinoma histology, prior docetaxel, castration-resistant disease, low-volume metastatic disease, or who cannot tolerate androgen receptor pathway inhibitors are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could expand treatment options by adding a new drug to standard androgen receptor pathway inhibitors with manageable side effects.

How similar studies have performed: Some trials combining novel agents with androgen receptor pathway inhibitors have shown promise, but xaluritamig appears to be a novel agent with limited prior human efficacy data.

Eligibility criteria

Inclusion Criteria:

* Participants must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted.
* Participants must have at the time of diagnosis:

  * De novo mHSPC, defined as metastatic disease with no prior diagnosis of localized prostate cancer AND started androgen deprivation therapy (ADT) (luteinising hormone-releasing hormone \[LHRH\] agonist/antagonist or orchiectomy) with or without androgen receptor pathway inhibitor (ARPI) (defined as abiraterone OR darolutamide) as SOC, first treatment with ADT should be no longer than 12 weeks before screening. Prior docetaxel treatment is not permitted.
* Participants must have at the time of diagnosis:

  * High-volume metastatic disease defined as presence of visceral metastasis and/or ≥ 4 bone metastases with at least one outside of the vertebral column and pelvis.
* Documented metastatic disease either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan.
* PSA not progressing per PCWG3 following the initial PSA nadir after starting ADT.

Exclusion Criteria:

* Prior history of central nervous system (CNS) metastases.
* Unresolved toxicities from prior anti-tumor therapy (excluding those related to ongoing ADT and ARPI) not having resolved to Common Terminology Criteria for Adverse events (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.
* Autoimmune disease requiring systemic immunosuppression within the past 2 years.
* Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active or systemic infection within 7 days prior to the first dose of study treatment.
* Prior six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.
* Prior radioligand therapy (RLT), poly-adenosine diphosphate ribose polymerase (PARP) inhibitor, cytotoxic chemotherapy, aminoglutethimide or ketoconazole for prostate cancer, or any prior systemic biologic therapy, including immunotherapy for prostate cancer.
* Prior enzalutamide or apalutamide within 15 days prior to enrollment.
* Requirement for chronic systemic corticosteroid therapy (prednisone dose greater than 10 mg per day or local equivalent) or any other immunosuppressive therapies (including anti TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing.
* Prior radiotherapy (to the prostate and/or to all visible metastatic lesions in a metastasis-directed therapy approach); palliative radiation within 2 weeks prior to first dose of study treatment is allowed.

Where this trial is running

San Francisco, California and 13 other locations

• University of California San Francisco — San Francisco, California, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (Recruiting)
• Thomas Jefferson University — Philadelphia, Pennsylvania, United States (Recruiting)
• Sarah Cannon Research Institute — Nashville, Tennessee, United States (Recruiting)
• Chris OBrien Lifehouse — Camperdown, New South Wales, Australia (Recruiting)
• Calvary Mater Newcastle Hospital — Waratah, New South Wales, Australia (Recruiting)
• Cabrini Hospital — Clayton, Victoria, Australia (Recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
• The Alfred Hospital — Melbourne, Victoria, Australia (Recruiting)
• Kantonsspital Graubuenden — Chur, Switzerland (Recruiting)
• Centre Hospitalier Universitaire Vaudois — Lausanne, Switzerland (Recruiting)
• Kantonsspital Sankt Gallen — Sankt Gallen, Switzerland (Recruiting)

Study contacts

• Study coordinator: Amgen Call Center

Conditions Metastatic Hormone-sensitive Prostate Cancer; Prostate cancer; Xaluritamig