The FDA has imposed a partial hold on U.S.-based enrollment of new patients in clinical trials of Epizyme’s lead candidate, the cancer treatment tazemetostat, after a patient in a Phase I pediatric study (NCT02601937) developed a secondary lymphoma.
Epizyme said the partial hold came after it submitted a safety report to the FDA and other regulators about the patient, who it acknowledged developed a secondary T-cell lymphoma. The patient “had advanced poorly differentiated chordoma,” according to the company.
“At the time of the safety report, the patient had been on study for approximately 15 months and had achieved a confirmed partial response. This patient has now discontinued tazemetostat and is being treated for T-cell lymphoma,” Epizyme stated.
Added Epizyme president and CEO Robert Bazemore: “Patient safety is of the utmost importance to Epizyme. We are working expeditiously with clinical trial investigators and regulatory authorities to initiate the appropriate steps to resume enrollment.”
The ill patient was the only instance of secondary lymphoma that has been observed across the tazemetostat clinical program, Epizyme said. More than 750 patients have been treated with tazemetostat to date.
“Doses explored in this study are higher than those in the company’s Phase II adult studies, an approach not uncommon to drug development in aggressive, difficult-to-treat pediatric cancers,” the company added.
According to Clinicaltrias.gov, tazemetostat is being assessed in 11 active studies that were recruiting patients at the time of the FDA hold, and three other studies that were active but not recruiting patients. Two other studies of tazemetostat were not yet recruiting patients.
Tazemetostat is a first-in-class enhancer of zeste homolog 2 (EZH2) inhibitor under study as a monotherapy in ongoing Phase I and II programs in solid tumors that include epithelioid sarcoma and other INI1-negative tumors; both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; mesothelioma; and combination studies in DLBCL and non-small-cell lung cancer.
“Epizyme, along with our global investigator community, has been very encouraged by the clinical responses and tolerability of tazemetostat observed in pediatric and adult patients with hematological malignancies and solid tumors enrolled in our trials,” Bazemore added. “We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer.”