Epizyme, Inc. announced updated safety and activity data from the Phase 1b safety run-in portion of its Phase 1b/3 confirmatory study evaluating the investigational use of tazemetostat, a first-in-class, oral, selective inhibitor of EZH2, in combination with rituximab + lenalidomide (R2) in patients with relapsed/refractory follicular lymphoma (R/R FL). These patients have been treated with at least one prior systemic therapy, including patients who are rituximab-refractory and/or relapsed within 24 months (POD24). These data will be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting on Saturday, June 4, 2022 during the Hematologic Malignancies Poster Session.

The updated interim analysis of the Phase 1b study includes 44 FL patients who received treatment with tazemetostat and R2 (400 mg [n=4], 600 mg [n=19], or 800 mg [n=21]) as of the January 22, 2022 data cutoff. The safety profile of the tazemetostat and R2 combination was consistent with the prescribing information for both tazemetostat and R2, respectively. Additionally, there was no clear dose response for treatment-emergent adverse events (TEAEs) or dose modifications.

Thirty-eight of the 44 patients were evaluable for tumor assessments as of the data cutoff, with 36 patients responding to treatment. The activity findings showed an objective response rate (ORR) of 95 percent (50% complete response [CR] rate and 45% partial response [PR] rate). Two patients achieved stable disease, and two patients had progressive disease (one from the 400-mg cohort and one from the 600-mg cohort).

Median progression-free survival (PFS) and duration of response were not yet reached as the study is ongoing. This analysis also provides more in-depth characterization of enrolled patients and their response to therapy. For patients who are rituximab-refractory the ORR was 100 percent (n=13), with six patients (46%) achieving a CR.

For patients with POD24, 100 percent (n=10) achieved an ORR, with four patients (40%) achieving a CR. For patients with wild type EZH2, the ORR was 94 percent (n=30), with 15 patients (47%) achieving a CR. For EZH2 mutation positive patients, the ORR was 100% (n=5), with three patients (60%) achieving a CR.

SYMPHONY-1 (EZH-302) is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase 1b/3 study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with R2 in patients with R/R FL after at least one prior line of therapy. The Phase 1b portion of the study is designed to determine the recommended Phase 3 dose (RP3D), activity, and safety of tazemetostat and R2. In addition to the safety run-in analysis, the study also assessed the pharmacokinetics and continues to assess clinical activity of tazemetostat when administered in combination with R2.