FDA Indications for Tazemetostat in R/R Follicular Lymphoma and Epithelioid Sarcoma Are Voluntarily Withdrawn

The FDA indications for tazemetostat (Tazverik) for the treatment of patients with relapsed or refractory follicular lymphoma and those with epithelioid sarcoma are being voluntarily withdrawn by the agent’s developer, Ipsen.¹

In an announcement, Ipsen noted that the decision to withdraw tazemetostat is effective immediately and applies to all approved indications. Specifically, tazemetostat was approved by the FDA for:²

• adult and pediatric patients 16 years of age and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
• adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation, as detected by an FDA-approved test, and who have received at least 2 prior systemic therapies.
• adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

The voluntary withdrawal is based on data from the ongoing phase 1b/3 SYMPHONY trial (NCT04224493), which is evaluating tazemetostat plus lenalidomide (Revlimid) and rituximab (Rituxan; R²) in patients with relapsed or refractory follicular lymphoma.^1,3 After reviewing data from the trial, an independent data monitoring committee concluded that risks for the safety of patients due to adverse effects (AEs) of secondary hematologic malignancies outweigh the benefits of tazemetostat.¹

Tazemetostat treatments in the trial have been stopped. Participating patients who are receiving the tazemetostat-based regimen will continue to receive R² alone. Enrollment for the study has been halted, although the study will stay open for long-term safety follow-up.

“While this is an extremely disappointing outcome, the safety of patients remains our priority,” Christelle Huguet, PhD, head of research and development for Ispen, stated in a news release. “Emerging data from this confirmatory study have highlighted a safety profile that is unfavorable compared [with] that previously observed in clinical evaluation. We will now work closely with investigators and clinical teams to support patients through the respective next steps and transition plans.”

What data supported the prior approvals of tazemetostat?

In June 2020, the FDA granted accelerated approval tazemetostat for the treatment of patients with relapsed/refractory follicular lymphoma whose tumors are EZH2 positive as detected by an FDA-approved test; and for those with relapsed/refractory follicular lymphoma who have no satisfactory alternative treatment options.³

The approval was supported by phase 2 E7438-G000-101 study (NCT01897571) which evaluated tazemetostat in patients with either follicular lymphoma that had EZH2 activating mutations (n = 45) or EZH2 wild-type disease (n = 54). Patients with EZH2 mutations achieved an overall response rate (ORR) of 69% (95% CI, 53%-82%), and those in the wild-type cohort experienced an ORR of 34% (95% CI, 22%-48%).

SYMPHONY was serving as the confirmatory trial to further support the accelerated approvals for patients with follicular lymphoma. The study was evaluating tazemetostat in combination with R2 vs R2 alone as second-line therapy for patients with relapsed/refractory follicular lymphoma.¹ EZH2 mutations were not required for patient enrollment; the study was powered to evaluate outcomes in both the EZH2-mutant and wild-type populations.

In January 2020, tazemetostat also received accelerated approval from the FDA for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.⁴

This regulatory decision was supported by data from cohort 5 of the phase 2 Study EZH-202 (NCT02601950), with data from this group showing that patients (n = 62) achieved an overall response rate of 15% (95% CI, 7%-26%) per RECIST 1.1 criteria, including a complete response rate of 1.6% and a partial response rate of 13%. The 6-month duration of response rate was 67%.

References

1. Ipsen voluntarily withdraws Tazverik (tazemetostat) in follicular lymphoma and epithelioid sarcoma. March 9, 2026. Accessed March 10, 2026. https://www.ipsen.com/press-release/ipsen-voluntarily-withdraws-tazverik-tazemetostat-in-follicular-lymphoma-and-epithelioid-sarcoma-3251503/
2. Batlevi CL, Salles G, Park SI, et al. Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma: phase 1b results of Symphony-1. Blood. 2022;140(suppl 1):2296-2298. doi:10.1182/blood-2022-166991
3. FDA granted accelerated approval to tazemetostat for follicular lymphoma. FDA. June 18, 2020. Accessed March 10, 2026. https://www.fda.gov/drugs/fda-granted-accelerated-approval-tazemetostat-follicular-lymphoma
4. FDA approves tazemetostat for advanced epithelioid sarcoma. FDA. January 24, 2020. Accessed March 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tazemetostat-advanced-epithelioid-sarcoma