Epizyme has posted updated data from the phase 2 trial it hopes will secure tazemetostat approval in epithelioid sarcoma. The data feature a slight uptick in objective responses offset by rises in the rates of some adverse events.
Massachusetts-based Epizyme filed for authorization of tazemetostat last week and arrived at the American Society of Clinical Oncology (ASCO) annual meeting armed with data it hopes will persuade the FDA to approve the EZH2 inhibitor. The ASCO data set features one more month of follow-up than the results shared by Epizyme at a previous cancer conference.
Over that month, another response caused the objective response rate (ORR) in treatment-naive patients to tick up from 21% to 25%. The ORR among the 38 patients with relapsed or refractory epithelioid sarcoma remained at 8%. ORR is the primary endpoint of the trial.
Patients with epithelioid sarcoma, an ultrarare soft tissue disease related to loss of the INI1 protein, have poor prospects, with median overall survival (OS) for metastatic forms of the condition coming in at under one year. Epizyme was yet to reach median OS in treatment-naive patients as of the ASCO data cutoff. As previously reported, the median OS in relapsed/refractory patients was 47.4 weeks.
Epizyme’s ASCO data featured bigger shifts in the safety data. The rate of grade 3 or higher treatment-emergent adverse events (TEAEs) remained at 13%, but there were increases in TEAEs of all grades.
In the ASCO data, 39% of patients suffered fatigue and 35% of subjects experienced nausea regardless of attribution. Those figures combine TEAEs and treatment-related AEs. Previously, Epizyme reported TEAEs alone. At the previous cutoff, the TEAE figure for both fatigue and nausea was 26%. Investigators reduced the dose given to two patients due to adverse events, and one patient dropped out because of an adverse event.
Epizyme is now waiting to learn whether the FDA will accept its filing for approval.
“The totality of these data formed the foundation for our first NDA submission. If we are successful, tazemetostat would be the first FDA-approved EZH2 inhibitor,” Epizyme Chief Medical Officer Shefali Agarwal said in a statement.
While working toward the regulatory nod, Epizyme is gearing up for a randomized controlled trial designed to secure full approval of tazemetostat. Epizyme plans to start the trial in the second half of the year but wants to reach “alignment” with the FDA and get the NDA accepted for review first.
Editor's note: This article was updated to clarify that the ASCO safety data featured treatment-emergent and treatment-related adverse events.