Epizyme reports positive data from Phase I trial of tazemetostat to treat non-hodgkin lymphoma

In NHL, treatment with tazemetostat continues to demonstrate an encouraging profile with nine of 15 evaluable NHL patients achieving an objective response, including a partial response in the first treated patient with an EZH2 tumor mutation. The data, which include patients from the dose escalation and dose expansion cohorts of the phase 1 study, as well as a food effects sub-study, were presented today by Vincent Ribrag, M.D., Institut Gustave Roussy, at the 13th International Conference on Malignant Lymphoma.

"The breadth, depth and durability of responses seen in NHL patients among multiple histologies continue to impress, as does the safety and tolerability of tazemetostat in this phase 1 study," said Dr. Ribrag.

"Among the patients in the dose escalation cohorts, we have seen a noteworthy deepening of responses over time, and in the first treated patient with an EZH2 tumor mutation, we have seen a partial response, which is very encouraging."

As of June 8, 2015, the following clinical data were observed:

• Nine of 15 evaluable NHL patients have achieved an objective response, including two patients with an ongoing complete response (CR).
• Five of nine evaluable diffuse large B-cell lymphoma (DLBCL) patients achieved an objective response. One patient with a CR remains on study at 18 months of treatment.
• Three of five evaluable patients with follicular lymphoma achieved an objective response. One patient with a CR remains on study at 13 months, and one patient with a PR remains on study at 13 months.
• One patient with a marginal zone lymphoma achieved a partial response and continues on study at 11 months.
• All treatment responses were observed between two and 10 months on therapy.
• One of 14 patients evaluated for EZH2 status possesses a specific EZH2 tumor mutation (Y646H). This patient, who had relapsed or been refractory to six previous treatment regimens, achieved a partial response after 16 weeks of therapy and remains on study.
• The majority of adverse events were grade 1 or grade 2 within the evaluable for safety population of 45 patients with NHL and solid tumors. The most common adverse events regardless of attribution were asthenia, anorexia, anemia, dyspnea and nausea. Five grade 3 or greater treatment-related adverse events were observed including one each of: grade 3 anorexia, grade 3 hypertension, grade 3 transaminase elevation, grade 4 thrombocytopenia, and grade 4 neutropenia.

"These results highlight the therapeutic potential of tazemetostat in NHL, with a number of patients achieving durable remissions with time on treatment at or beyond one year," said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. "We look forward to exploring further the clinical utility of tazemetostat in NHL in a robust phase 2 development program."

The NHL patients enrolled on study were heavily pre-treated, with 85 percent of patients having received three or more prior therapies and 37 percent of patients having received more than five or more prior therapies. Thirty-seven percent of patients were refractory to their last prior regimen and 26 percent of patients had received a prior autologous hematopoietic stem cell transplant.

Drug pharmacokinetics showed rapid absorption with a mean terminal half-life of three to five hours. Cmax and AUC1-12hr were dose proportional at steady-state throughout the dosing range. Steady-state Ctrough levels were reached by day 15.

The company plans to report a further update from the phase 1 trial by the end of 2015.

This open-label, multi-center, phase 1 study is investigating tazemetostat as monotherapy in patients with relapsed or refractory B-cell non-Hodgkin lymphomas or advanced solid tumors. The study objectives include identification of the recommended phase 2 dose or maximum tolerated dose, safety, tolerability, pharmacokinetics and preliminary evaluation of anti-tumor activity.

Five cohorts were studied in the dose escalation phase: 100 mg, 200 mg, 400 mg, 800 mg and 1600 mg; and two cohorts, 800 mg and 1600 mg, were evaluated in the dose expansion phase. All doses were given twice daily.