Elraglusib Earns FDA Rare Pediatric Disease Designation for Ewing Sarcoma

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The FDA has awarded rare pediatric disease designation to the novel GSK-3β inhibitor elraglusib (9-ING-41) as a potential therapeutic option for patients with Ewing sarcoma.¹

The ongoing, open-label, multicenter phase 1/2 Actuate-1902 trial (NCT04239092) is evaluating the safety and efficacy of elraglusib for the treatment of pediatric patients with relapsed/refractory malignancies, including Ewing sarcoma and Ewing sarcoma–related pediatric small round cell sarcomas. The study has enrolled 8 patients with relapsed/refractory Ewing sarcoma who have been treated with elraglusib in combination with topotecan and cyclophosphamide.

“Receiving rare pediatric disease designation from the FDA underscores the urgent need for new treatment options for patients with Ewing sarcoma and recognizes elraglusib’s transformative potential,” Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, stated in a news release. “Early clinical data from [the] ongoing phase 1/2 trial show promising antitumor activity with objective tumor responses, including 2 ongoing durable complete responses [reported] in the first 6 patients treated with relapsed/refractory Ewing sarcoma, reinforcing our confidence in elraglusib’s potential impact in this challenging disease setting. We are committed to advancing elraglusib’s clinical development with the ultimate goal of providing new therapeutic options where current approaches are unsatisfactory.”

The ongoing phase 1/2 trial is enrolling patients up to 22 years of age with recurrent or refractory malignancies.² Investigators are excluding patients with extra-cranial germ-cell tumors showing elevated serum tumor markers, brain stem tumors, or central nervous system (CNS) germ-cell tumors with abnormal tumor markers. Participants must have either measurable or evaluable disease with no known curative therapy available. Patients over 16 years of age need to have a Karnofsky performance status of at least 50%, and those 16 years of age or younger need to have a Lansky performance status of at least 50.

All toxicities from prior therapies must be resolved to an acceptable level, and participants must have undergone at least 1 previous treatment regimen. Adequate organ and bone marrow function are also required.

Exclusion criteria include hypersensitivity to study drugs, uncontrolled illness, significant retinal disease, other malignancies under active treatment, pregnancy, recent organ transplantation, or current participation in another clinical trial.

Elraglusib is being evaluated at 9.3 mg/kg twice per week as monotherapy; in combination with irinotecan; in combination with irinotecan and temozolomide (Temodar); and in combination with cyclophosphamide and topotecan.

Safety is the trial’s primary end point.

In September 2024, Actuate Therapeutics announced data from the trial showing that elraglusib generated preliminary signals of antitumor activity when combined with chemotherapy for the treatment of pediatric patients with relapsed/refractory Ewing and Ewing-related sarcomas.³

Additionally, in September 2024, the FDA granted orphan drug designation to the novel inhibitorfor the treatment of patients with soft tissue sarcomas.⁴

Topline data from phase 1 of the phase 1/2 Actuate-1902 trial are expected in the second half of 2025.¹

References

1. Actuate announces FDA rare pediatric disease designation granted to elraglusib for treatment of Ewing sarcoma. News release. November 12, 2024. Accessed November 12, 2024. https://actuatetherapeutics.com/press_releases/actuate-announces-fda-rare-pediatric-disease-designation-granted-to-elraglusib-for-treatment-of-ewing-sarcoma/
2. 9-ING-41 in pediatric patients with refractory malignancies. ClinicalTrials.gov. Updated November 8, 2024. Accessed November 12, 2024. https://clinicaltrials.gov/study/NCT04239092
3. Actuate Therapeutics obtains complete responses and provides updates on clinical trial of elraglusib for the treatment of relapsed/refractory Ewing sarcoma. News release. Actuate Therapeutics, Inc. September 9, 2024. Accessed November 12, 2024. https://actuatetherapeutics.com/press_releases/actuate-therapeutics-obtains-complete-responses-and-provides-update-on-clinical-trial-of-elraglusib-for-the-treatment-of-relapsed-refractory-ewing-sarcoma/
4. Actuate receives FDA orphan drug designation for elraglusib for treatment of soft tissue sarcomas. News release. Actuate Therapeutics, Inc. September 11, 2024. Accessed November 12, 2024. https://www.globenewswire.com/news-release/2024/09/11/2944428/0/en/Actuate-Receives-FDA-Orphan-Drug-Designation-for-Elraglusib-for-Treatment-of-Soft-Tissue-Sarcomas.html