EWSR1 Immunotherapy in Ewing Sarcoma and DSRCT

Summary

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 botensilimab (4 doses after each EWSR1 immunotherapy shot) and balstilimab (an infusion every 2 weeks), these are 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.

Conditions

• Ewing Sarcoma
• Desmoplastic Small Round Cell Tumor

Interventions

DRUG

EWSR1 immunotherapy

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.

DRUG

Botensilimab

Participants will receive Botensilimab (anti-CTLA-4) at 1 milligram per kilogram (mg/kg) intravenously (through an IV) on Weeks 0, 4, 12, and 24.

DRUG

Balstilimab

Participants will receive Balstilimab (anti-PD1) at 3 milligram per kilogram (mg/kg) intravenously (through an IV) on Week 0 and then every 2 weeks for 6 months.

Sponsors & Collaborators

• The Little Warriors Foundation

  collaborator UNKNOWN

• Rabi Hanna

  lead OTHER

Principal Investigators

• Rabi Hanna, MD · Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

• Peter M Anderson, MD, PhD · Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

• Matteo Trucco, MD · Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

• Timothy A Chan, MD, PhD · Case Comprehensive Cancer Center, Cleveland Clinic Center for Immunotherapy and Immuno-Oncology

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-31

Primary Completion

2029-10-31

Completion

2030-07-31

FDA Drug

Yes

Countries

• United States

Study Locations