Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Recurrent Alveolar Rhabdomyosarcoma, Recurrent Ewing Sarcoma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Refractory Alveolar Rhabdomyosarcoma, Refractory Ewing Sarcoma, Refractory Lymphoma, Refractory Malignant Solid Neoplasm

In brief

This phase I/II trial tests the safety, best dose, and whether elimusertib works in treating patients with solid tumors that have come back (relapsed) or does not respond to treatment (refractory). Elimusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT05071209

Run by

National Cancer Institute (NCI)

People needed

31

Starts

2021-12-22

Expected to finish

2026-03-31

Last updated by the study team

2026-01-23

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Part A: Patients between >= 12 months and < 18 years of age
• Part B:
• Patients between >= 12 months and =< 30 years of age for the phase 2 expansion cohorts for both EWS and PAX3-FOXO1 ARMS.
• Patients between >= 12 months and =< 21 years of age for the phase 2 DDR expansion cohort
• The Phase 2 cohorts will initially open concurrently with the Phase 1 portion but will only enroll patients at least 18 years of age. Patients < 18 years of age will be included in the Phase 2 cohorts only after the RP2D/MTD has been estimated in the Phase 1 portion
• All patients for both Parts A and B must have a minimum body surface area (BSA) >= 0.74 m\^2
• All patients for both Parts A and B must have the ability to swallow BAY 1895344 (elimusertib) tablets intact
• Patients with recurrent or refractory solid tumors. Patients must have had histologic verification of malignancy at original diagnosis or relapse
• Part A: Any (non-CNS primary) solid tumor diagnosis including lymphoma which meets one of the following criteria:
• Any Ewing Sarcoma (histological confirmation alone is adequate) or any EWS-fusion positive solid tumor (i.e. including related Ewing's family of tumors with EWS fusions such as EWS-WT1, EWS-ATF1, etc.)
• Alveolar rhabdomyosarcoma (ARMS) with the PAX3-FOXO1 fusion. This does not include PAX7-FOXO1 or other variant fusion ARMS. Please note that a FISH showing FOXO1 breakapart is NOT sufficient for eligibility onto this cohort since it cannot distinguish between FOXO1 partners
• Any (non-CNS primary) solid tumor including lymphoma with inactivating alterations of any of the DNA Damage Repair (DDR) genes: ATM, ATRX, BRCA1, BRCA2, CDK12, CHEK1, CHEK2, FANCA, MSH2, MRE11, PALB2, PARP1, POLD1, RAD51, or XRCC2
• Part B: Any (non-CNS primary) solid tumor diagnosis including lymphoma which meets one of the following criteria:
• B1, EWS Cohort:
• Any Ewing Sarcoma (histological confirmation alone is adequate) or any EWS-fusion positive solid tumor (i.e. including related Ewing's family of tumors with EWS fusions such as EWS-WT1, EWS-ATF1, etc.)
• B2, PAX3-FOXO1 ARMS Cohort:
• Alveolar rhabdomyosarcoma (ARMS) with the PAX3-FOXO1 fusion. This does not include PAX7-FOXO1 or other variant fusion ARMS. Please note that a FISH showing FOXO1 breakapart is NOT sufficient for eligibility onto this cohort since it cannot distinguish between FOXO1 partners
• B3, DDR Non-statistical Cohort:
• Any (non-CNS primary) solid tumor including lymphoma with inactivating alterations of any of the DNA Damage Repair (DDR) genes: ATM, ATRX, BRCA1, BRCA2, CDK12, CHEK1, CHEK2, FANCA, MSH2, MRE11, PALB2, PARP1, POLD1, RAD51, or XRCC2
• All the genes on the DDR panel are annotated with OncoKB, a precision oncology knowledge base which is publicly available here: https://www.oncokb.org/. Alterations which are categorized either 'Oncogenic' or 'Likely Oncogenic' would be considered sufficient for eligibility on either the phase 1 or phase 2 portions of this study. Alterations which are not annotated in OncoKB will need to be reviewed with locally qualified experts in molecular pathology, such as via an established molecular tumor board, in order to determine the likely oncogenicity AND will require approval by the study chair, Dr. Michael Ortiz. If such experts are not available at any institution, the study chair will review
• In cases where multiple mutations are present or multiple samples are available, either at different locations or different points in time, the presence of a single qualifying genomic alteration in any of those samples will is considered sufficient for eligibility on the phase 2 portions of this study
• Qualifying aberrations must be detected in either DNA or ribonucleic acid (RNA) in any tumor tissue sample (i.e. detection of a variant on circulating tumor DNA/RNA is not sufficient to qualify) using a somatic (and/or germline) mutational testing approach with either a targeted panel or whole exome/genome sequencing in the context of a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory setting. Any CLIA certified laboratory is acceptable to use
• Part A: Patients must have either measurable or evaluable disease
• Part B (1, 2, 3): Patients must have measurable disease
• Patients with a prior history of CNS metastases may enroll on study provided there is no current evidence of active disease at the time of enrollment

You may not qualify if…

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and for 3 months + 2 days for males and 6 months + 2 days for females after receiving the last dose of BAY 1895344 (elimusertib) on the study. Abstinence is an acceptable method of birth control. Female patients must not breastfeed during treatment and until 4 months after last study drug administration
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Drugs that are considered sensitive or narrow therapeutic range CYP3A4 substrates should be avoided for the duration of protocol therapy
• Dedicated CNS imaging is not required but patients with current active CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, will be excluded from study participation
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• UCSF Medical Center-Mission Bay — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States
• University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States
• Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Nationwide Children's Hospital — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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