Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses response to tazemetostat in children with

The EZH2 inhibitor tazemetostat showed promising antitumor activity in a phase I study of pediatric patients with 

-negative rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma tumors. This phase I study showed several responses, which are not commonly seen this early, Chi says. These responses included complete responses (CRs). Three patients had a CR, while 1 had a partial response, and 5 had stable disease. These findings, Chi says, are encouraging moving into a phase II study.

Additionally, Chi notes that a company investing their time, energy, and money into a small pediatric study of a rare tumor type such as rhabdoid tumors or 

deficient tumors is encouraging. This small experimental study was completed with a relatively quick turnaround time, she adds.

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Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses response to tazemetostat in children with INI1-negative tumors.

Dr. Chi on Response to Tazemetostat in Children With INI1-Negative Tumors

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses the EZH2 inhibitor tazemetostat in pediatric patients with 

In a phase I study of pediatric patients with 

-negative rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma tumors, tazemetostat showed promising antitumor activity. Chi reports that the drug was very well-tolerated, and the side effects seen were nausea, vomiting, and a small amount of bone marrow suppression. Tolerability is important for these children, as they have previously undergone intensive regimens of chemotherapy and radiation, Chi adds.

There was 1 case of a secondary malignancy. Chi says that she and her fellow investigators are currently evaluating this case. They are working on determining the relationship with the inhibitor and how it can be prevented in the future. Still, these findings have led to a phase II trial, where tazemetostat will be given at a recommended dose of 1200 mg/m

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses the EZH2 inhibitor tazemetostat in pediatric patients with INI1-negative tumors.
 

Dr. Chi on Tazemetostat in Pediatric Patients With INI1-Negative Tumors

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses a trial of tazemetostat in pediatric patients with 

The EZH2 inhibitor tazemetostat was evaluated in a phase I study of pediatric patients with

-negative rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma tumors. In the study, 46 patients were treated with 7 dose levels in this dose-escalation portion of the phase I trial, ranging from 240 mg/m

Results presented at the 2018 ASPHO Conference showed that tazemetostat had promising antitumor activity in these patients, with 3 patients achieving a complete response, 1 achieving a partial response, and 5 having stable disease. There was 1 side effect of a secondary T-cell lymphoma. Chi says that they are currently investigating this and are working it up to see what the relationship is, and how it might be preventable in the future. This secondary malignancy led the FDA to halt enrollment in April 2018.

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses a trial of tazemetostat in pediatric patients with INI1-negative tumors.
 

Dr. Chi Discusses Tazemetostat Trial in INI1-Negative Pediatric Tumors

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses pediatric atypical teratoid rhabdoid tumors (ATRTs).

ATRTs are rare central nervous system tumors, explains Chi. This tumor is distinct, as it only has 1 specific mutation in its DNA in a gene called

. Rhabdoid tumors of the kidney and of the soft tissues have a very similar type of mutation, Chi says. Other tumor types in this category include epithelioid sarcoma, renal cell medullary carcinoma, and chordomas.

The EZH2 inhibitor tazemetostat is currently being investigated in pediatric patients with 

-negative rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma tumors. Patients in the phase I dose-escalation portion of the study were treated with 7 dose levels, ranging from 240 mg/m

 of tazemetostat given twice daily. So far, antitumor activity has been shown with tazemetostat in these patients.

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses pediatric atypical teratoid rhabdoid tumors. 

Dr. Chi Discusses Pediatric Atypical Teratoid Rhabdoid Tumors

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of pediatrics, Harvard Medical School, discusses a phase I multicenter trial of tazemetostat in children with INI1-negative tumors.

Investigators are evaluating the EZH2 inhibitor tazemetostat in children with relapsed or refractory INI1-negative tumors including rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma. The use of tazemetostat in this population makes sense, explains Chi, as EZH2 is one unit in a multi-unit complex called polycomb repressive complex 2 (PRC2). PRC2 works antagonistically to the SWI/SNF complex, of which INI1 is a member.

This is the first time that tazemetostat has been used in children, and the first time that EZH2 has been tested in children. In the phase I trial, tazemetostat was dosed continuously as an oral suspension administered twice daily in patients aged 6 months to 21 years. Chi says that this has been a collaborative effort, and the study is now moving into a dose-expansion phase based on positive safety signals in the phase I trial.

Susan N. Chi, MD, senior physician, director, Pediatric Brain Tumor Clinical Trials Program, Dana-Farber Cancer Institute, assistant professor of Pediatrics, Harvard Medical School, discusses a phase I multicenter trial of tazemetostat in children with INI1-negative tumors.
 

Susan N. Chi, MD

Articles

Dr. Chi on Response to Tazemetostat in Children With INI1-Negative Tumors

Dr. Chi on Tazemetostat in Pediatric Patients With INI1-Negative Tumors

Dr. Chi Discusses Tazemetostat Trial in INI1-Negative Pediatric Tumors

Dr. Chi Discusses Pediatric Atypical Teratoid Rhabdoid Tumors

Dr. Chi on Study of Tazemetostat in Children With INI1-Negative Tumors