Xaluritamig is a T cell engager that recruits the immune system to prostate tumors that express the target STEAP1. It has shown lasting benefit in almost half of metastatic castration-resistant prostate cancer patients, leading to ongoing phase 3 trials. Due to the difficulty of sampling tumor tissue from metastatic patients, it is now known who will respond to xaluritamig and why. It is also unknown how xaluritamig may work in earlier patients, including newly diagnosed patients with localized disease, to promote cure.
This proposal leverages deep analysis of tumor tissues and circulating tumor cells in the blood, with which the team has extensive expertise, and applies this to a pre-operative xaluritamig clinical trial for newly diagnosed prostate cancer patients before surgery. The team proposes to understand how variation or “heterogeneity” in the types of tumor cells may influence xaluritamig response. The team also aims to identify newly generated or “primed” T cells that recognize tumor, and a favorable balance between cooperating myeloid immune cells that can either activate or inhibit immune responses, in xaluritamig responders.
If successful, this work will for the first time identify pre-treatment markers for patients who will respond to xaluritamig therapy, and other targets that can also be treated to help xaluritamig work in the half of patients who do not respond. This work will also justify the use of earlier xaluritamig at first diagnosis of localized prostate cancer to delay or prevent recurrence, a step towards possible cure.
Projects and Grants
Mechanisms of immune priming in responding patients to neoadjuvant xaluritamig in prostate cancer
