prifetrastat

Prifetrastat is an oral, small‑molecule epigenetic inhibitor of the histone lysine acetyltransferases KAT6A and KAT6B, developed by Pfizer for the treatment of hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer that has progressed after CDK4/6 inhibitor‑based endocrine therapy.[1][4][9][15] By selectively inhibiting KAT6A/B catalytic activity, prifetrastat reduces acetylation of histone H3 at lysine 23 (H3K23), downregulates estrogen receptor expression, and is designed to overcome endocrine and CDK4/6 inhibitor resistance in ER‑positive disease.[1][11][13][15] In a first‑in‑human phase 1 study, prifetrastat demonstrated a tolerable safety profile and promising antitumor activity, particularly in combination with fulvestrant (objective response rate ~37% and median progression‑free survival ~10.7 months at the selected 5 mg once‑daily dose), leading to ongoing global phase 3 evaluation versus everolimus‑based endocrine therapy in this setting.[1][3][4]

Other names

prifetrastat