Susan N. Chi, MD
Tazemetostat showed promising antitumor activity in pediatric patients with INI1
-negative rhabdoid tumors, epithelioid sarcoma, chordoma, and synovial sarcoma tumors, according to findings presented at the 2018 ASPHO Conference.
, Chi, director, Pediatric Neuro-Oncology and Clinical Trials, Dana-Farber Cancer Institute, discussed the rationale for using tazemetostat in this pediatric population, as well as the future steps being taken with this treatment.
OncLive: Can you provide an overview of the study?
I have a particular interest in patients with atypical teratoid rhabdoid tumors (ATRTs), which are very rare central nervous system tumors. This is a tumor that is distinct, in that it only has one specific mutation in its DNA in this gene called INI1
. There are other tumors that have a very similar type of mutation, and those are rhabdoid tumors of the kidney and rhabdoid tumors of the soft tissues. Other tumors types include epithelioid sarcoma, renal cell medullary carcinoma, and chordomas.
This is the first time that this drug has been used in children, and it is the first time EZH2 inhibition has been tested in children, as well. We have collaborated with multiple institutions and investigators, along with Epizyme, to work on this phase I study in children.
What is the design of this trial?
This is what they call a Rolling 6 design, which means that, at any given time, up to 6 children will be enrolled onto the dose-escalation phase. There are 2 phases—dose escalation and dose expansion. We completed the dose-escalation phase, which we started at a relatively lower dose, and continued to escalate until there was either intolerance to the medication, or biologically with regard to pharmacokinetics and pharmacodynamic measurements—which indicated we were hitting our target. We reached a dose measurement of 1200 mg/m2, by which all of those criteria were met. We are now currently in the dose-expansion phase.
What findings can you share thus far?
So far, we know that this is a very well-tolerated medication. The types of side effects that we see are nausea, vomiting, and very little in the way of bone marrow suppression, which is very important for these children who have previously had a very intensive regimen of chemotherapy drugs and radiation therapy.
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