CHICAGO, Illinois and FORT WORTH, Texas — Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), today announced results from the phase 1 portion of its phase 1/2 clinical study evaluating elraglusib as a monotherapy or in combination with irinotecan, irinotecan plus temozolomide, or with cyclophosphamide plus topotecan in pediatric patients with refractory malignancies (Actuate-1902; NCT 04239092).
The Actuate-1902 trial was an open-label, multicenter phase 1/2 study evaluating the safety and efficacy of elraglusib in 40 pediatric patients ages 3 – 21 with relapsed (>2 remissions)/refractory cancers, including Ewing sarcoma (EWS), neuroblastoma, Central Nervous System (CNS) tumors, non-EWS sarcomas, and other refractory pediatric malignancies.
Importantly, data from the Phase 1 trial showed clinical responses in relapsed/refractory EWS, which is viewed as positive evidence of clinical activity in this difficult-to-treat indication. Following initial responses observed in the Actuate-1902 clinical study, the Company plans to advance clinical development of elraglusib in children, adolescents, and adults with relapsed/refractory EWS, while assessing collaborative development programs in neuroblastoma and other pediatric indications with leading pediatric consortia and Key Opinion Leaders to align future studies with patient needs and regulatory expectations.
“Elraglusib continues to exhibit the potential to extend and improve the lives of patients in disease settings where specific treatment options are extremely limited,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “In the 1902 trial, we observed early signals of significant efficacy in EWS, neuroblastoma and Desmoplastic Small Round Cell Tumor (DSRCT), showing that elraglusib’s unique mechanism of action can play an important role in multiple difficult-to-treat cancers. We plan to initiate additional clinical trials in 2026 that expedite a registration pathway for the program in patients with Ewing sarcoma and potentially advancing elraglusib in neuroblastoma”.
Actuate-1902 Key Study Highlights
- Elraglusib in combination with Cyclophosphamide and Topotecan Regimen:
- Clinical responses and disease control observed in 10 of 19 patients with relapsed/refractory Ewing sarcoma and neuroblastoma.
- One patient with six prior treatments for EWS achieved a CMR with Partial Response (PR) (60% reduction in tumor size) of a lung target lesion. The patient completed 30 weeks (Cycle 10) on treatment. Long term treatment with elraglusib monotherapy is continuing without disease progression outside of the study.
- One patient with four prior treatments for EWS (+EWSR1 translocation) was identified as a CR (BOR) at week 9 (Cycle 3) with CT showing a 100% decrease in piriformis muscle tumor compared to baseline (CMR by PET).
- One patient with six prior treatments for unfavorable neuroblastoma histology (Indeterminate MYCN, ALK, and ploidy) had a first response at week 9 (Cycle 3) of stable disease (SD), with a best overall response (BOR) of complete bone marrow response identified at week 27 (Cycle 9).
- One patient with 10 prior treatments for DSRCT achieved a PR (52.6% decrease in liver/lung target lesions compared to baseline). Non-target lesions included multiple lung and liver lesions, which were not present at the end of treatment.
- Six patients (osteosarcoma, anaplastic ependymoma, glioblastoma multiforme, and four EWS) with prior treatments ranging from 2 to 11, achieved BORs of stable disease.
- Clinical responses and disease control observed in 10 of 19 patients with relapsed/refractory Ewing sarcoma and neuroblastoma.
- Elraglusib in combination with Irinotecan Regimen:
- Four patients (neuroblastoma, ganglioneuroblastoma (a high-risk variant with an unfavorable prognosis)) achieved BOR of stable disease.
- One patient with neuroblastoma achieved a 35% reduction in tumor burden between baseline and week 9 (Cycle 3).
- One patient with ependymoma experienced stable disease with a prolonged time to progression of 54 weeks.
- Four patients (neuroblastoma, ganglioneuroblastoma (a high-risk variant with an unfavorable prognosis)) achieved BOR of stable disease.
About Actuate-1902
Actuate-1902 was an open-label, multicenter phase 1/2 study evaluating the safety and efficacy of elraglusib in forty (40) pediatric patients ages 3 to 21 with relapsed (>2 remissions)/refractory cancers, including EWS, neuroblastoma, CNS tumors, non-EWS sarcomas, and other refractory pediatric malignancies. The phase 1 dose escalation portion of the trial was designed primarily to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of elraglusib as a single agent and in combination with chemotherapy. While an MTD was not reached, initial evidence of anti-tumor activity was observed, particularly when elraglusib is administered with a standard cyclophosphamide and topotecan regimen. The phase 1 portion of this study was closed in July 2025.
About Ewing Sarcoma
Ewing sarcoma (EWS) is a small round blue cell tumor defined by a recurring cytogenetic fusion event involving the Ewing sarcoma breakpoint region 1 gene (EWSR1) and the Erythroblast Transformation Specific (ETS) transcription family. EWS is derived from primordial bone marrow–derived mesenchymal stem cells, which originate in bone and soft tissue and constitute the second most common bone tumor in children and adolescents, most commonly occurring in white adolescents with a median age of 15 years.
For patients with metastatic disease up-front, 5-year survival remains low at 13-30%. The risk of relapse is notable, regardless of upfront disease status, at 30-40% with local disease and 60-80% with primary metastatic disease. Post-relapse, survival is approximately 20% and although new therapeutic approaches have been attempted, there has been no improvement in the prognosis of relapsed EWS. The development of novel therapeutics and clinical trials is essential to advance the prognosis of relapsed/refractory EWS.
About Neuroblastoma
Neuroblastoma is a type of cancer that originates in nerve tissue of the adrenal gland, neck, chest, or spinal cord. This type of cancer often begins in early childhood, usually in children younger than 5 years of age. Sometimes, neuroblastoma forms before birth and is found during a fetal ultrasound. Usually, however, neuroblastoma is diagnosed after it has metastasized. This form of cancer spreads most often to the lymph nodes, bones, bone marrow, liver, and in infants, skin. Approximately 650 children in the United States are diagnosed with neuroblastoma each year, according to estimates from the National Cancer Institute.
About Actuate Therapeutics, Inc.
Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate’s lead investigational drug, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and DNA Damage Response (DDR). Elraglusib may also mediate anti-tumor immunity through the regulation of multiple immune checkpoints and immune cell function. For additional information, please visit the Company’s website at http://www.actuatetherapeutics.com.
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