Symptoms and General Pathology

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Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

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Sarcoma

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Sarcoma, Ewing

Rhabdomyosarcoma

Rhabdomyosarcoma, Alveolar

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Neoplasms, Connective and Soft Tissue

Myosarcoma

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Lymphosarcoma

Ewing Sarcoma

Rhabdomyosarcoma Alveolar

Patients receive elimusertib PO BID on days 1-3, 8-10, 15-17, and 22-24 of each cycle. Treatment repeats every 28 days for 26 cycles in the absence of disease progression or unacceptable toxicity.

Elimusertib

Michael V Ortiz

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.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BAY 1895344 (elimusertib) administered as an oral tablet, twice per day for 3 days on and 4 days off to patients \< 18 years of age with recurrent or refractory Ewing sarcoma (and EWS fusions), PAX3-FOXO1 alveolar rhabdomyosarcoma, and non-central nervous system (CNS) solid tumors or lymphoma with specific deleterious deoxyribonucleic acid (DNA) damage response (DDR) pathway alterations. (Phase 1/Part A) II. To define the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients and young adults with recurrent or refractory Ewing sarcoma (and EWS fusions). (Phase 2/Part B) III. To define the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients and young adults with recurrent or refractory PAX3-FOXO1 fusion positive alveolar rhabdomyosarcoma. (Phase 2/Part B) IV. To define and describe the toxicities of BAY 1895344 (elimusertib) administered on this schedule. (Phase 1/Part A)

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetics of BAY 1895344 (elimusertib) in children and adolescents with recurrent or refractory cancer.

II. To assess the biologic activity of BAY 1895344 (elimusertib) by immunohistochemical assessments of phosphorylated (p)ATR, pH2AX, and pKAP1 in paired tissue samples before and after treatment with BAY 1895344 (elimusertib).

III. To assess whether the activity of BAY 1895344 (elimusertib) is influenced by alternative lengthening of telomeres (ALT), as well as tumor tissue expression of ATM, PGBD5, and/or R-loops.

IV. To assess whether the activity of BAY 1895344 (elimusertib) is associated with tumor mutational processes, as measured by whole genome tumor tissue sequencing.

V. To preliminary determine the anti-tumor activity of BAY 1895344 (elimusertib) in children \< 18 years of age within the confines of a phase 1 study (Phase 1 and 2/Part A and B).

VI. To assess the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients with non-CNS solid tumors or lymphomas with specific deleterious alterations in DDR pathway genes. (Phase 2/Part B)

OUTLINE: This is pediatric a phase I, dose-escalation study as well as a phase II dose expansion study in pediatric patients and young adults.

Patients receive elimusertib orally (PO) twice daily (BID) on days 1-3, 8-10, 15-17, and 22-24 of each cycle. Treatment repeats every 28 days for 26 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 12 months, every 6 months for 24 months, and then annually for up to 60 months.

Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors

A Phase 1/ 2 Study of BAY 1895344 (Elimusertib, NSC#810486) in Pediatric Patients With Relapsed or Refractory Solid Tumors

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Frequency (%) of patients experiencing a cycle 1 dose limiting toxicity among toxicity-evaluable patients stratified by dose level.

Frequency (%) of patients with best response of complete response or partial response among response-evaluable patients stratified by Phase 2 cohort.

Frequency (%) of patients with adverse events stratified by study part and dose level.

Median (min, max) of the area under the drug concentration time curve (AUC) in cycle 1 stratified by study part and dose level.

Median (min, max) of the change in pKAP1 stratified by study part and dose level.

Spots Global Cancer Trial Database for refractory alveolar rhabdomyosarcoma