Rabi Hanna
This study is for people who have high-risk Ewing sarcoma (ES), or a related Ewing's family tumor, desmoplastic small round cell tumor (DSRCT). The purpose of this study is to see if a new EWSR1 immunotherapy (a lipid nanoparticle coated with EWSR1 mRNA) which is given as a shot is safe and whether it can help the body's immune system better recognize and fight cancer. This EWSR1 immunotherapy is designed to target a specific genetic change (EWSR1 fusion gene) that is found in cancer cells but not in normal, healthy cells. Because the EWSR1 gene is broken in cancer cells and the small protein it makes are only in the ES or DSRCT cancer cells, the goal of EWSR1 immunotherapy is to help the immune system identify and attack the cancer without harming normal cells. It is not yet approved by the Food and Drug Administration (FDA). EWSR1 immunotherapy will be given as a shot into the muscle of the arm, leg, or buttock. If participants also receive pembrolizumab (an infusion every 2 weeks), it is given intravenously (IV) by a needle in the arm over 30 minutes. Participants in this study will receive treatment for about 6 months or until their cancer gets worse. Participants will remain in the study for follow-up for an additional year, for a total time of about 1.5 years in the study.
Ewing sarcoma (ES) is an aggressive type of cancer that has a high risk of spreading to other parts of the body. Even though it often responds well to chemotherapy and radiation at first, it still carries the risk of coming back and/or spreading. Children and young adults whose cancer is limited to one area generally have a better outlook with overall survival at about 75%. However, outcomes are much worse for adults and for people whose cancer has already spread, returned after treatment, or relapsed. In these groups, overall survival is only about 15-25%. People with relapsed or metastatic E…
Inclusion Criteria: * Participants must have histologically confirmed Ewing sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) and confirmation of fusion gene rearrangement and breakpoint EWSR1-FLI1, EWSR1-ERG, EWSR1-WT1, who have completed standard of care vincristine + doxorubicin + cyclophosphamide alternating with ifosfamide + etoposide (VDC/IE) and have relapsed or had metastatic disease or are very high-risk disease (Bosma groups C, D, E, and/or very poor necrosis after VDC/IE) are eligible. All EWSR1 immunotherapy monotherapy participants are expected to have completed standar…
Participants will receive EWSR1 immunotherapy at 50 micrograms (mcg) (or 25 mcg for children 12 years and younger) through an intramuscular injection on Weeks 0, 4, 12 and 24.
Participants will receive Pembrolizumab (anti-PD1) at 3 milligram per kilogram (mg/kg) intravenously (through an IV) on Week 0 and Week 4.