Preliminary data from an ongoing, global, phase II trial of tazemetostat, a first-in-class EZH2 inhibitor, in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) showed “encouraging” safety and efficacy, according to lead author Franck Morschhauser, MD, PhD, who presented the findings at the 2016 ASH Meeting on Lymphoma Biology.
“These patients, especially those with highly refractory disease or multiple relapses, are in need of new options,” Dr. Morschhauser, from Hôpital Claude Huriez in Lille, France, told ASH Clinical News. “Preliminary findings suggest that continued tazemetostat treatment has the potential to translate into tumor regression over a prolonged period of time.”
Dr. Morschhauser said that results from this open-label, two-stage study are consistent with the earlier phase I study in which researchers observed many patients who had partial responses moving to complete responses over time.
The ongoing phase II trial is evaluating tazemetostat 800 mg taken orally twice daily in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) with mutated or wild-type EZH2. All patients had relapsed/refractory disease following at least two prior treatment regimens (including at least 1 alkylator and anti-CD20-based regimen); DLBCL patients were included if they were considered unable to benefit from autologous hematopoietic cell transplantation.
The study’s primary endpoint is objective response rate (including complete response [CR], partial response [PR], and stable disease [SD]) assessed every eight weeks for the first six months and every 12 weeks thereafter. Secondary endpoints include progression-free survival, duration of response, and safety/tolerability.
Dr. Morschhauser presented interim results for 47 patients who had evaluable efficacy data available by the cut-off date. Patients were stratified into five cohorts based on tumor subtype:
- EZH2-mutated DLBCL with germinal center B-cell (GCB) subtype (n=5): 1 PR and 2 SD
- DLBCL with GCB subtype and wild-type EZH2 (n=19): 2 CR, 1 PR, and 6 SD
- DLBCL with non-GCB subtype (n=20): 2 CR, 4 PR, and 5 SD
- FL with EZH2 mutations (n=3): 3 PR
The fifth cohort included patients with FL with wild-type EZH2, but assessment data were not available at the cut-off date and were not included in this analysis.
At the cut-off date, the four patients who achieved a CR and the majority of patients who achieved a PR or SD as a best response were still on tazemetostat treatment.
“Consistent with the phase I experience, the frequency of grade ≥3 treatment-emergent adverse events (TEAEs) is low at 16 percent,” the authors reported. The most common TEAEs (≥5%) were nausea, asthenia, thrombocytopenia, neutropenia, and fatigue; seven of these AEs were grade 3 or higher. Safety is “critically important as we consider treating patients over an extended period of time,” Dr. Morschhauser said. “In addition, we have seen a strong correlation between tazemetostat treatment and clinical benefits in patients, even in those who have been heavily pre-treated.”
“Patients continue to be followed for clinical outcomes in light of observations from phase I that the onset of clinical response may occur over as many as 10 months and continue to improve for patients who remain on treatment,” the authors concluded.
Morschhauser F, Salles G, McKay, P et al. 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 (NHL). Abstract #88525. Presented at the 2016 ASH Meeting on Lymphoma Biology, June 20, 2016; Colorado Springs, CO.