FDA Orders Enrollment Hold on Tazemetostat Clinical Trials

FDA Orders Enrollment Hold on Tazemetostat Clinical Trials

Patient enrollment for clinical trials of Epizyme’s tazemetostat is temporarily on hold. The decision from the U.S. Food and Drug Administration (FDA) follows a safety report of a pediatric patient who developed a secondary lymphoma while being treated with the investigational medication.

Specifically, this partial clinical hold includes patients with genetically defined solid tumors and blood-related cancers, while Epizyme updates the trials’ informed consent, protocols, and the investigator’s brochure.

Patients already enrolled and without disease worsening will be able to continue receiving tazemetostat. But the company will need to add some modifications in line with the FDA requirements before resuming patient recruitment in the U.S.

The safety report was submitted by Epizyme to the FDA and other regulatory agencies. It regarded a patient in the company’s Phase 1 trial (NCT02601937) with advanced chordoma, a type of malignant bone and soft tissue tumor called sarcoma, who developed a secondary T-cell lymphoma. This form of non-Hodgkin’s lymphoma is frequently aggressive and can be fast-growing.

The company observed that tazemetostat’s doses tested in this trial are higher than those in the Epizyme’s Phase 2 studies in adult patients. This strategy is not uncommon in clinical trials of aggressive, difficult-to-treat pediatric cancers, Epizyme noted.

The company added that, at the time of the safety report, the patient had been treated for nearly 15 months and had achieved a confirmed partial response, which means a reduction in tumor size or cancer extent in response to treatment. The patient now has stopped taking tazemetostat and is being treated for the T-cell lymphoma.

Cancer therapies, including chemotherapy and radiation treatment, may cause secondary malignancies, according to Epizyme. This is the only case of secondary lymphoma in more than 750 patients treated with tazemetostat across the company’s clinical program, Epizyme wrote in a press release.

T-cell lymphoma is included as a potential adverse event in trial protocols and also is part of the informed consent and the investigator’s brochure.

“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,” said Robert Bazemore, president and CEO at Epizyme.

“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. We remain encouraged by the potential of tazemetostat to address the unmet needs of many patients living with cancer,” Bazemore added.

Tazemetostat (EPZ-6438) is an inhibitor of the EZH2 enzyme, which is involved in tumor progression by making changes in the DNA that affect gene expression. Recent results of the first part a Phase 1/2 clinical trial (NCT01897571) showed that treatment of relapsed or refractory B-cell NHL with tazemetostat was safe and shrank tumors in 38 percent of patients.

Epizyme also is studying monotherapy with tazemetostat in certain solid tumors, including epithelioid sarcoma; follicular lymphoma, and diffuse large B-cell lymphoma (both are forms of NHL); mesothelioma, and; non-small cell lung cancer.

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