Epizyme announced new and positive data from its ongoing Phase 2 clinical trial evaluating the safety and efficacy of orally administered tazemetostat in relapsed or refractory patients with non-Hodgkin’s lymphoma.
The findings were presented at the 2016 American Society of Hematology Meeting on Lymphoma Biology in a study titled “Initial report from a phase 2 multi-center study of tazemetostat (EPZ-6438), an inhibitor of enhancer of zeste-homolog 2 (EZH2), in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.”
“Patients with relapsed or refractory NHL are often faced with limited treatment options, particularly those who are highly refractory or whose disease is multiply relapsed as we have seen in this study population,” Franck Morschhauser, MD, PhD, from the Centre Hospitalier Régional Universitaire de Lille, France, and Phase 2 primary investigator, said in a press release.
“These patients are in need of new therapeutic options, and while these data are early, we are encouraged and look forward to further understanding the impact that tazemetostat could have on patients as the trial proceeds,” Morschhauser added.
Tazemetostat is an orally administered small molecule that inhibits EZH2, an enzyme whose abnormal activity in some cancers leads to a misregulation of genes involved in cell proliferation, resulting in the rapid growth of cancer cells.
The Phase 2, five-arm, multicenter and global study includes several populations of patients with relapsed or refractory non-Hodgkin’s lymphoma, divided by EZH2 mutation status and cell-of-origin: diffuse large B-cell lymphoma (DLBCL) with Germinal Center B-cell (GCB) subtype and EZH2 mutations; DLBCL with GCB subtype and wild-type EZH2; DLBCL with non-GCB subtype; follicular lymphoma (FL) with EZH2 mutations; and follicular lymphoma with wild-type EZH2.
The study’s primary endpoint is overall response rate, and secondary endpoint include duration of response and progression-free survival.
All cohorts have surpassed futility, except the follicular lymphoma with wild-type EZH2 cohort that has not yet reached futility assessment, as confirmed by Epizyme’s Independent Data Monitoring Committee. This is a means of evaluating whether the results of a trial are unlikely to result in significant changes, even after recruiting more patients, indicating that it should be stopped.
Trial recruitment is on track and consistent with incidence rates of non-Hodgkin’s lymphoma subtypes, with approximately 20 percent of DLBCL GCB and follicular lymphoma patients having EZH2 mutations. Across all five cohorts, 82 patients have been assessed for tazemetostat safety and 47 were evaluated for efficacy.
The safety profile was consistent with that of the Phase 1 trial for tazemetostat, with the majority of the adverse events being classified as grade 1 or grade 2.
Regarding tazemetostat efficacy, several patients were found to have either objective responses or stable disease in response to the treatment. At the time of analysis, among the five patients with DLBCL with GCB subtype and EZH2 mutations, one showed partial response and two had stable disease.
From the 18 patients included in the DLBCL with GCB subtype and wild-type EZH2, two showed a complete response, one partial response, and six stable disease; in the 20-patient group with DLBCL with non-GCB subtype, there were two complete response, four partial response, and five stable disease; all three patients included in the cohort follicular lymphoma with EZH2 mutations showed partial response.
The majority of patients were still on tazemetostat treatment at the time of the data cutoff, and Epizyme continues to enroll non-Hodgkin’s lymphoma patients into its Phase 2 trial.
“We are pleased by the performance of tazemetostat in the Phase 2 trial so far, which has been consistent with our Phase 1 results,” said Peter Ho, M.D., Ph.D., executive vice president and chief medical officer at Epizyme. “We have observed patients receiving clinical benefit from tazemetostat and continue to believe that prolonged exposure to treatment has the potential to result in decreased tumor burden over time.”