On Monday, April 23, the United States Food and Drug Administration (FDA) issued a temporary clinical hold, meaning a pause in enrollment, on US-based trials studying the drug tazemetostat. Two of these trials were enrolling chordoma patients — a Phase 2 trial for adults, and a Phase 1 trial for pediatric patients.
The hold was initiated following submission of a safety report by Epizyme, the manufacturer of tazemetostat, to the FDA and other regulatory authorities, about a pediatric patient with poorly differentiated chordoma in the company’s Phase 1 pediatric study who developed a secondary T-cell lymphoma. At the time of the safety report, the patient had been enrolled in the trial for approximately 15 months and had achieved a confirmed partial response. The patient has now discontinued tazemetostat and is being treated for T-cell lymphoma.
As stated in Epizyme’s press release, secondary malignancies are a known risk associated with many cancer therapies, including chemotherapy and radiation treatment. T-cell lymphoma is identified as a possible adverse event in tazemetostat trial protocols and the informed consent provided to all patients when they enroll in the study. Of the 750 patients who have been treated with tazemetostat so far, this is the only case of secondary lymphoma that has been observed. And although this case is a chordoma patient, there is no evidence that the development of a secondary malignancy is linked to chordoma specifically.
Placing a hold on enrollment for a trial is a typical action taken by the FDA when there is a safety concern reported to allow time to evaluate the concern. Epizyme is currently working with the clinical trial investigators and the FDA to update the trial protocol and the informed consent to reflect this new information which will require approval by the Institutional Review Board (IRB) at each trial site. Their goal is to begin re-opening trial sites for enrollment as soon as possible; this should take at least several months.
As of now, all US enrollment to tazemetostat trials — for both adult and pediatric patients — are on hold. Outside the US, however, tazemetostat trial sites are still enrolling adult patients. Patients currently enrolled in the study who have not experienced disease progression will continue to receive tazemetostat.
- Read Epizyme’s announcement about the hold »
- Read OncLive piece about the FDA’s decision »
- Read CF’s description of the tazemetostat trials:
- Contact a CF Patient Navigator for more information »