Tazemetostat Benefits Follicular and B-cell Lymphoma Patients with EZH2 Mutations, Phase 2 Trial Shows

Tazemetostat Benefits Follicular and B-cell Lymphoma Patients with EZH2 Mutations, Phase 2 Trial Shows

Twelve of 13 patients with relapsed or refractory follicular lymphoma (FL) and mutations of the EZH2 enzyme responded either fully or partially to treatment with tazemetostat, according to a Phase 2 clinical trial.

Tazemetostat, Epizyme’s EZH2 enzyme inhibitor, also benefited patients with diffuse large B-cell lymphoma ( DLBCL) and the mutations.

In addition, half of follicular lymphoma patients with no EZH2 mutations either responded to the therapy or achieved a stable disease.

Epizyme presented the findings at the 14th International Conference on Malignant Lymphoma in Lugano, Switzerland, June 14-17. The presentation was titled “Interim Report from a Phase 2 Multicenter Study of Tazemetostat, an EZH2 Inhibitor, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas.

“These interim data findings represent an important step forward for our tazemetostat program, with anti-tumor activity observed across all groups of the study,” Rob Bazemore, chief executive officer of Epizyme, said in a press release. “The activity we have observed in patients with an EZH2 mutation exceeds what we have seen so far with wild-type EZH2, consistent with our scientific hypothesis, and we are encouraged by both the objective responses [full and partial responses] and durability of responses in FL and DLBCL.”

“Our focus is on continuing to increase enrollment of patients with an EZH2 mutation [in clinical trials], and engaging with FDA [the U.S. Federal Drug Administration] in the second half of the year to determine potential registration paths to bring tazemetostat to patients as quickly as we can,” Bazemore added.

Tazemetostat was designed to inhibit the EZH2 enzyme, which plays a role in tumor progression. Previous  studies and clinical trials have demonstrated its anti-cancer activity and safety.

Epizyme is in the midst of testing tazemetostat’s effectiveness, safety and tolerability in a Phase 1/2 trial (NCT01897571).

Preliminary results of the Phase 2 part of the trial showed that all 13 FL patients with EZH2 mutations achieved at least a stable disease with tazemetostat. Twelve of the patients, or 92 percent, responded either partially or completely to treatment, and one achieved a stable disease.

Response rates were also promising among the 54 FL patients with a normal EZH2 protein. Fourteen, or 26 percent, responded to treatment, and 23, or 43 percent, achieved a stable disease.

Meanwhile, five of 17 DLBCL patients with EZH2 mutations responded to treatment — 29 percent. And 35 percent achieved a stable disease.

Among DLBCL patients without EZH2 mutations, the response rates were lower, with only 18 out of 119, or 15 percent, responding.

“I believe that tazemetostat may play a significant role in disease management for my patients, and am particularly excited by the impact observed in patients with follicular lymphoma,” said Dr. Franck Morschhauser, a professor at the Centre Hospitalier Régional Universitaire in Lille, France, who was the lead investigator of the study.

“I am also encouraged by the level of activity in DLBCL patients with EZH2 mutations, especially in light of the bleak prognosis associated with advanced disease. Tazemetostat has demonstrated a uniquely tolerable safety profile, and I look forward to further exploring its full benefit in patients with relapsed or refractory FL and DLBCL as the data mature,” Morschhauser added.

Overall, the treatment was well tolerated. So far, only 3 percent of the patients have had to reduce their dose and 2 percent have had to discontinue their treatment due to adverse events. The most common adverse events were nausea, low blood platelet counts, anemia, and cough.

Another study that Epizyme presented at the conference showed that non-Hodgkin lymphoma patients with EZH2 mutations and faulty MYD88 mutations also respond well to tazemetostat.

In addition, the research showed that EZH2 mutations can be detected in circulating tumor DNA — that is, DNA material in the blood. This suggests that a simple blood test could determine whether a patient has an EZH2 mutation or not. That would help doctors select which patients would be more likely to respond to tazemetostat.

The presentation was titled “Preliminary Evidence of a Molecular Predictor of Tazemetostat Response, Beyond EZH2 Mutation, in NHL Patients Via Characterization of Archive Tumor and Circulating Tumor DNA.

Tazemetostat received U.S. Food and Drug Administration fast track status in November 2016 for treating DLBCL patients with EZH2 mutations. In May 2017 it granted the designation to tazemetostat as a treatment for refractory FL patients, regardless of their EZH2 status.

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