20230005 A Phase III Study of Xaluritamig Compared to Cabazitaxel or Second Androgen Receptor-Directed Therapy in Patients with Advanced, Metastatic, Castration-Resistant Prostate Cancer

Résumé de l'étude

A total of approximately 675 participants will be enrolled from about 150–200 hospitals/facilities in Europe, North America, Asia, and Australia, randomized in a 2:1 ratio (450:225 patients) to receive either Xaluritamig as monotherapy (test group) or Cabazitaxel or a second androgen receptor-directed therapy (ARDT) at the discretion of the investigator (control group). Approximately 22 patients are planned for the study in Switzerland. Randomization will be stratified by: • either low or high lactate dehydrogenase (LDH) • presence of liver metastases (yes versus no) • previous treatment with PSMA (prostate-specific membrane antigen) radioligand therapy (yes versus no) • planned treatment according to the intention-to-treat principle (ITT) with Cabazitaxel versus second ARDT Enrollment in the ITT groups with Cabazitaxel versus second ARDT will be distributed equally (i.e., 50%/50%) across the two stratification factors. The study may last up to approximately 56 months for each patient, including a screening phase of up to 28 days, a treatment phase, and a follow-up phase lasting approximately 36 months. The actual treatment duration depends on how well patients tolerate or respond to the study treatments. The study will end 3 years after the last patient is randomized. After treatment, safety follow-up visits will occur 30 (+3) days after the last dose of the study drug, with long-term follow-up visits every 8 weeks (± 7 days) for the first 12 months and then every 12 weeks (± 14 days) for up to 3 years.

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Intervention étudiée

Patients will be randomly assigned to different treatment arms. There is a 2:3 chance of receiving Xaluritamig and a 1:3 chance of being assigned to the control arm with standard therapy (Cabazitaxel or second ARDT at the dosage according to regionally approved schemes or practice guidelines), with the standard therapy determined by the investigator after eligibility criteria are met and screening examinations are completed. The first dose of the study drug must be administered ≤ 10 days after randomization.

If patients are assigned to the Xaluritamig group, they will receive the study drug in the first treatment month once weekly as a short infusion directly into the vein, each lasting approximately 60 minutes. The dose will be gradually increased in 3 steps until the target dose of 1.5 mg is reached. After reaching the target dose, patients will receive Xaluritamig every 2 weeks (Day 1 and Day 15) for the remainder of the treatment duration.

In the standard treatment group, patients will receive either daily Abiraterone or Enzalutamide tablets to take or Cabazitaxel as a one-hour intravenous infusion directly into the vein every 3 weeks, depending on the physician's recommendation.

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Maladie en cours d'investigation

Xaluritamig works by activating the body's immune system to combat cancer growth. In particular, Xaluritamig helps activate T-cells (a type of immune cell) to attack prostate cancer cells by creating a connection between proteins that are only present on the surface of certain types of T-cells and specific prostate cancer cells. The aim of the study is to compare the safety and efficacy of Xaluritamig with other standard therapies such as chemotherapy (Cabazitaxel) or androgen receptor-directed therapy (ARDT – Abiraterone acetate or Enzalutamide) in patients with metastatic castration-resistant prostate cancer (mCRPC). Xaluritamig is based on preclinical data and clinical evidence for efficacy with a manageable safety profile in patients with mCRPC (first-in-human study). Based on the available data, Xaluritamig is being developed as an option to improve treatment outcomes and survival in mCRPC with prior taxane treatment.

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Sponsor

Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz

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Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Commission cantonale de Zurich

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Date d'approbation du comité d'éthique

29.04.2025

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Résultats de l'essai