tazemetostat + doxorubicin

**tazemetostat + doxorubicin** is an investigational combination cancer therapy under clinical development as frontline treatment for advanced epithelioid sarcoma. Tazemetostat is a selective small molecule inhibitor of **Enhancer of zeste homolog 2 (EZH2)**, a histone methyltransferase involved in transcriptional repression and epigenetic modification, particularly in tumors with loss of the tumor suppressor INI1/SMARCB1. Doxorubicin is a conventional anthracycline chemotherapy agent that intercalates DNA, inhibits topoisomerase II, and generates free radicals causing cytotoxicity in rapidly dividing cells. This combination aims to synergize epigenetic modulation (targeted therapy with tazemetostat) with cytotoxic DNA damage (chemotherapy with doxorubicin) to enhance antitumor efficacy in sarcoma. The combination is currently being evaluated in a phase 3, randomized, double-blind, placebo-controlled clinical trial for patients with unresectable or metastatic epithelioid sarcoma, with tazemetostat administered orally at 800 mg twice daily and doxorubicin intravenously at 75 mg/m^2 every 21 days for up to 6 cycles[1][5][9].