A Phase 3 Study of Xaluritamig versus Cabazitaxel or Second Androgen Receptor-Directed Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Chemotherapy

The primary objective of this study is to compare overall survival in subjects with metastatic castration-resistant prostate cancer receiving xaluritamig versus investigator's choice of cabazitaxel or a second androgen receptor-directed therapy. Secondary objectives include:

• Comparison of radiographic progression-free survival and other measures of efficacy.
• Evaluation of biochemical response and symptomatic skeletal events.
• Assessment of safety, tolerability, and patient-reported safety outcomes.
• Evaluation of health-related quality of life.
• Characterization of pharmacokinetics and assessment of immunogenicity.

This study involves 331 male participants diagnosed with metastatic castration-resistant prostate cancer. The study population includes individuals aged between 18 and 65 years. Eligible subjects must have histological or pathological confirmation of adenocarcinoma of the prostate and exhibit evidence of progressive disease based on PCWG3 criteria. Participants are required to have received prior androgen-deprivation therapy and demonstrate castrate levels of serum testosterone. Selection is based on the requirement of prior progression on at least one androgen receptor-directed therapy and having undergone exactly one taxane therapy within the metastatic castration-resistant setting. Additionally, subjects must possess an Eastern Cooperative Oncology Group performance status of 0 or 1 and maintain adequate organ function.

This Phase 3, open-label, multicenter, randomized study is designed to evaluate the efficacy of xaluritamig compared to an investigator's choice of cabazitaxel or a second androgen receptor-directed therapy. The trial is conducted in subjects with metastatic castration-resistant prostate cancer who have previously received chemotherapy. The primary endpoint is overall survival. Secondary endpoints include radiographic progression-free survival, objective response, and various patient-reported outcomes. The study is estimated to take place between February 2025 and November 2029. The research methodology involves assigning participants to either the investigational test product or a comparator arm to determine clinical benefit.

The investigational product is xaluritamig (AMG 509), which is administered as a solution for infusion via intravenous use.

The comparator treatments include cabazitaxel, administered via intravenous use, and abiraterone acetate or enzalutamide, which are administered via the oral route.

Siltuximab (SYLVANT) is utilized as a background therapy and is provided as a powder for concentrate for solution for infusion for intravenous use.

The primary efficacy endpoint for this study in subjects with metastatic castration-resistant prostate cancer is overall survival. Secondary efficacy assessments include radiographic progression-free survival, objective response, duration of response, disease control, and time to response, all evaluated according to modified RECIST v1.1 via blinded independent central review. Additional secondary parameters involve time to first symptomatic skeletal events and PSA50 and PSA90 responses.

The evaluation of patient-reported outcomes includes assessments of pain and functional status using the following instruments:

• Brief Pain Inventory - Short Form, measuring worst pain score, pain intensity scale, and pain interference scale.
• Functional Assessment of Cancer Therapy – Prostate, measuring total and subscale scores.
• European Quality of Life - 5 Domain 5 Level Scale, specifically the Visual Analogue Scale.