abivertinib + abiraterone

Abivertinib + abiraterone is a combination therapy currently in phase 2 clinical trials for metastatic castration-resistant prostate cancer (mCRPC), specifically in patients who harbor the adrenal-permissive HSD3B1(1245C) allele. Abivertinib is a third-generation small molecule tyrosine kinase inhibitor (TKI) that targets epidermal growth factor receptor (EGFR), Bruton tyrosine kinase (BTK) receptor, and bone marrow tyrosine kinase gene on chromosome X (BMX). It irreversibly inhibits BTK and BMX, preventing phosphorylation necessary for androgen biosynthesis in prostate cancer. Abiraterone acetate is a small molecule androgen biosynthesis inhibitor that blocks CYP17A1, reducing androgen production that fuels prostate tumor growth. The rationale for this combination is abivertinib’s ability to block BMX-mediated phosphorylation of the 3βHSD1 enzyme, a step that supports extragonadal androgen biosynthesis even with CYP17 blockade, and abiraterone’s established activity in inhibiting androgen synthesis pathways, together aiming for deeper suppression of residual androgen production in advanced, resistant disease[1][2][4].

Other names

abivertinib + abiraterone acetateabivertinib plus abirateroneMAVERICK combination