Epizyme publishes Phase 1 Tazemetostat study in The Lancet Oncology
Epizym announced its first-in-human data on the effects of EZH2 inhibition in patients with advanced solid tumors and B-cell non-Hodgkin lymphoma was published in the peer-reviewed The Lancet Oncology. The objectives of the Phase 1 dose-escalation portion of the study were to evaluate the safety and tolerability of orally dosed tazemetostat, a first-in-class selective inhibitor of EZH2. The study established the recommended dose for the Phase 2 expansion study and demonstrated favorable safety findings and anti-tumor activity. The open-label Phase 1 study was designed to evaluate the maximally tolerated dose and supported defining the recommended Phase 2 dose of tazemetostat. Tazemetostat was dosed twice daily as a single agent in patients with relapsed or refractory B-cell NHL or with advanced solid tumors including molecularly defined INI1- or SMARCA4-negative tumors. Additional study objectives were to evaluate the adverse events, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of the agent. The results of the safety, PK and PD analyses helped determine the RP2D of 800 mg twice daily. The most common treatment-related adverse events, regardless of attribution, were grade 1 or 2 asthenia, anorexia, anemia, muscle spasms, nausea and vomiting. One single dose-limiting toxicity of grade 4 thrombocytopenia was identified at the highest dose of 1600 mg, but no other grade 3 or 4 toxicities were observed at a frequency greater than 5%.