Lymphoma Hub spotlight | SYMPHONY-1: A phase Ib/III trial of TAZ+Len+R in R/R FL

⭐Lymphoma Hub spotlight | SYMPHONY-1: A phase Ib/III trial of TAZ+Len+R in R/R FL⭐

Tazemetostat is a first-in-class oral EZH2 inhibitor approved by the U.S. Food and Drug Administration (FDA) for adult patients with relapsed/refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2^mut and have received ≥2 prior systemic therapies or who have no satisfactory alternative treatment options.¹

The SYMPHONY-1 trial is a phase Ib/III, double blind, placebo-controlled study of tazemetostat with lenalidomide and rituximab in R/R FL. The primary endpoints were to determine recommended phase III dose and progression-free survival in patients with wild-type and EZH2^mut R/R FL.^1,2 Results showed that the combination was well tolerated, with an 800 mg twice daily dose of tazemetostat recommended for phase III. At 22.5 months, the overall response rate was 90.9%, with a complete response rate of 54.8%. The ORR was consistent across subgroups, including patients with wild-type or EZH2^mut and those who were rituximab refractory or sensitive. The median progression-free survival and duration of response were not reached, with 18-month PFS estimates of 79.5% (intent-to-treat) and 94.4% (800 mg cohort). The safety profile was consistent with prior data, with neutropenia as the most common severe adverse event. The phase III trial enrolling ~500 patients is ongoing, with primary completion expected in early 2026.¹