This research study involves a combination of three drugs given together as a possible treatment for these types of cancers. One drug is small molecule inhibitor targeting EZH2 (tazemetostat) and two are immunotherapeutic checkpoint inhibitors (nivolumab and ipilimumab). This is a Phase I/II clinical trial. Phase I clinical trials test the safety of an investigational drug, or combination of drugs, and tries to define the appropriate dose of the investigational drugs to use for further studies. Phase II clinical trials test the safety and effectiveness of an investigational drug, or drug combination, to learn whether the drug or drug combination works in treating a specific disease. Investigational means that the drug combination is being studied.~This trial is studying the combination of tazemetostat, nivolumab, and ipilimumab in two parts:~Part 1: To find the safest dose of these three study drugs in combination for children with INI1- (or SMARCA4-) negative cancers who have completed upfront treatment~Part 2: To determine whether this combination can effectively treat INI1- or SMARCA4-negative cancers~The research study procedures include screening for eligibility study treatment, evaluation and follow-up visits. Participants will be asked to provide blood samples and undergo procedures that might be different from a regular medical examination. There are additional research samples that participants will be asked to consent for their collection.~Participants will receive study treatment for up to 2 years, as long as there is benefit or there are no serious side effects. Participants will be followed for approximately 2 years after stopping treatment.~It is expected that about 49 people will take part in this research study.~The U.S. Food and Drug Administration (FDA) has not approved this combination of three drugs for this specific disease. However, tazemetostat has been approved for use in epithelioid sarcoma (an INI1-deficient tumor), and the combination of nivolumab and ipilimumab has also been approved for other uses. Separately, tazemetostat and the combination of nivolumab and ipilimumab have also been tested in children and the safest doses of each drug (and the combination for nivolumab and ipilimumab) have been determined.~Bristol-Myers Squibb and Epizyme, two pharmaceutical companies, are supporting this study by providing the study drugs. Dana-Farber Cancer Institute is also supporting this study by providing funding.
This research study involves a combination of three drugs given together as a possible treatment for malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, epithelioid sarcoma, chordoma or other tumors that are deficient in one of two possible proteins, either INI-1 (SMARCB1) or SMARCA4.~The names of the study drugs involved in this study are:~Tazemetostat (TAZVERIK)~Nivolumab (OPDIVO)~Ipilimumab (YERVOY)