tildrakizumab + abiraterone acetate

Tildrakizumab is a humanized IgG1/kappa monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23), inhibiting its interaction with the IL-23 receptor. In a novel therapeutic approach for metastatic castration-resistant prostate cancer (mCRPC), tildrakizumab is being evaluated by the Institute of Cancer Research (ICR) in combination with abiraterone acetate, a small molecule inhibitor of the CYP17A1 enzyme. The rationale for this combination, currently in the Phase I/II ACTION trial, stems from preclinical evidence that tumor-infiltrating inflammatory myeloid cells release IL-23, which activates the JAK2-STAT3 signaling pathway in prostate cancer cells to promote tumor growth and confer resistance to androgen receptor-targeting therapies. By blocking IL-23, the combination aims to reverse this resistance and improve outcomes for patients who have progressed on abiraterone alone.

Brand names

IlumyaZytigaIlumetriYonsa

Other names

Abiraterone in Combination with TildrakizumabACTION trial combinationAnti-IL-23 monoclonal antibody + CYP17 inhibitor