The FDA has granted Rare Pediatric Disease Designation to elraglusib (9-ING-41), a novel GSK-3β inhibitor, for the potential treatment of Ewing sarcoma. This designation underscores the critical need for innovative therapeutic options for this challenging pediatric cancer.
The ongoing, open-label, multicenter phase 1/2 Actuate-1902 trial (NCT04239092) is evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including Ewing sarcoma and Ewing sarcoma–related pediatric small round cell sarcomas. The trial has enrolled eight patients with relapsed/refractory Ewing sarcoma who are being 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," said Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, 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 phase 1/2 trial includes patients up to 22 years of age with recurrent or refractory malignancies. Key exclusion criteria involve 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.
Elraglusib Dosing and Trial Endpoints
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. The primary endpoint of the trial is safety.
Preliminary Antitumor Activity
In September 2024, Actuate Therapeutics announced data from the trial demonstrating preliminary signals of antitumor activity when elraglusib was combined with chemotherapy for the treatment of pediatric patients with relapsed/refractory Ewing and Ewing-related sarcomas.
Orphan Drug Designation
In addition to the Rare Pediatric Disease Designation, the FDA granted orphan drug designation to elraglusib in September 2024 for the treatment of patients with soft tissue sarcomas.
Topline data from phase 1 of the phase 1/2 Actuate-1902 trial are expected in the second half of 2025.
