Tazemetostat Withdrawn From Follicular Lymphoma, Sarcoma Markets

Tazemetostat (Tazverik) has been voluntarily withdrawn as a treatment for all approved indications, including follicular lymphoma and epithelioid sarcoma, according to a news release from the developer, Ipsen.¹

Of note, the decision to withdraw the agent was based on findings from the phase 1b/3 SYMPHONY-1 trial (NCT04224493), which evaluated rituximab (Rituxan) and lenalidomide (Revlimid) alone or with tazemetostat among patients with follicular lymphoma. An independent data monitoring committee (IMDC) suggested that due to the emergence of secondary hematologic malignancies with the combination, the potential risks may outweigh the benefits for patients.

Additionally, the developers are undergoing steps to discontinue treatment for patients currently enrolled on the trial, with patients switching over to standard-of-care lenalidomide/rituximab. Investigators will keep the study open to continue assessing the long-term safety outcomes of all patients. However, all active clinical trials and expanded access programs including tazemetostat will be discontinued.

“While this is an extremely disappointing outcome, the safety of patients remains our priority,” Christelle Huguet, PhD, executive vice president and head of Research and Development at Ipsen, said in the release.¹ “Emerging data from this confirmatory study have highlighted a safety profile that is unfavorable compared to 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.”

Investigators in the SYMPHONY-1 trial evaluated the combination regimen vs standard-of-care treatment among those with relapsed/refractory follicular lymphoma. The study served as a confirmatory trial required under the accelerated approval pathway for tazemetostat in this disease state. Patients were evaluated across 229 sites in 15 countries.²

Those treated were randomly assigned to receive lenalidomide as 20 mg capsules or 10 mg capsules if creatinine clearance was less than 60 mL/minute daily on days 1 to 21 of each 28-day cycle for 12 cycles and rituximab at 375 mg/m² intravenously on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2 to 5. In the phase 1b portion of the trial, patients in the investigational arm were treated with escalating doses of tazemetostat from 400 mg to 800 mg orally twice daily in 28-day cycles per a standard 3+3 design. In the phase 3 portion of the trial, tazemetostat was given at 800 mg twice daily in 12 continuous 28-day cycles, followed by an additional 2 years at the same schedule if tolerated.

The primary end point of the study was the recommended phase 3 dose in the 1b portion of the study. In the phase 3 portion of the trial, it was progression-free survival in both the wild-type and mutant-type populations. Secondary end points included pharmacokinetics, complete response rate, objective response rate, overall survival, duration of response, and safety.

Patients 18 years and older with histologically confirmed grade 1 to 3A follicular lymphoma; at least 1 prior line of systemic chemotherapy, immunotherapy, or chemoimmunotherapy; and measurable disease per Lugano classification were eligible for enrollment on the trial.

Tazemetostat previously received accelerated approval from the FDA among adult patients with relapsed/refractory follicular lymphoma with EZH2-mutant disease who received at least 2 prior therapies, in addition to patients with no satisfactory alternative options, in June 2020.³ The agent was also approved for patients 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection in January 2020.⁴

References

1. Update: Ipsen voluntarily withdraws Tazverik® (tazemetostat) in follicular lymphoma and epithelioid sarcoma. News release. Ipsen. March 9, 2026. Accessed March 9, 2026. https://tinyurl.com/3sdsxmc9
2. A study to assess the efficacy, safety, pharmacodynamics, and pharmacokinetics of tazemetostat in combination with lenalidomide plus rituximab versus placebo in combination with lenalidomide plus rituximab in adult patients at least 18 years of age with relapsed/​refractory follicular lymphoma. (SYMPHONY-1). ClinicalTrials.gov. Updated March 2, 2026. Accessed March 9, 2026. https://tinyurl.com/mrnkzft3
3. FDA granted accelerated approval to tazemetostat for follicular lymphoma. News release. FDA. June 18, 2020. Accessed March 9, 2026. https://tinyurl.com/5h4bsf5p
4. FDA approves tazemetostat for advanced epithelioid sarcoma. News release. January 23, 2020. Accessed March 9, 2026. https://tinyurl.com/38kekfyd