EHA 2018 | Outcomes of the phase II study of tazemetostat in patients with R/R FL

On Friday 15^th June an oral abstract session took place at the 23^rd congress of the European Hematology Association (EHA). Abstract S100 was presented by Gilles Salles, South Lyon University Hospital Complex, Lyon, on the interim update of the phase II study of tazemetostat in patients with relapsed/refractory (R/R) follicular lymphoma (FL).

Tazemetostat is a selective, reversible, oral inhibitor of mutated and wild-type EZH2. It has shown activity and acceptable safety profiles as monotherapy in phase I and II studies in R/R non-Hodgkin lymphoma (NHL).

Study Overview

• Multi-center, open-label study in 6 cohorts of patients who have had ≥2 lines of therapy
• The primary endpoint was objective response rate (ORR) and secondary endpoints were progression-free survival (PFS), duration of response (DOR), safety and tolerability
• The outcomes of this study were focused on patients with R/R FL
• Patients received 800mg of tazemetostat twice daily until disease progression or withdrawal

Key Findings

• Patients evaluable for efficacy = FL wild-type (WT) EZH2 (n=54) and FL mutated (MT) EZH2 (n=28)
  • The ORR for FL EZH2 MT = 71% (n=20) vs FL EZH2 WT = 33% (n=18)
  • The overall ORR was 46%
• Out of the 28 patients with FL EZH2 MT, 100% had evidence of tumor reduction vs 77.5% of patients with FL EZH2 WT
• Patients evaluable for safety (n=82)
  • The most frequent treatment-emergent adverse events (AEs) grade ≥3 were thrombocytopenia (6%), anemia (6%), asthenia (4%) and fatigue (2%)
  • The most frequent treatment-related AEs grade ≥3 were thrombocytopenia (4%), anemia (4%), asthenia (1%) and fatigue (1%)

Dr Salles concluded his talk by stating that the interim data of this study demonstrated clinical activity of tazemetostat in R/R FL patients with previous lines of therapy. It showed durable clinical responses and also that tazemetostat was well tolerated. These promising findings support EZH2 as a potential novel therapeutic target in R/R FL.