CHICAGO, Illinois and FORT WORTH, Texas – Actuate Therapeutics, Inc. (NASDAQ: ACTU), 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), provided an update on its Phase 1/2 trial of elraglusib in relapsed/refractory Ewing Sarcoma (r/r EWS).
“Ewing sarcoma is a highly metastatic form of sarcoma and the second most prevalent primary malignant tumor in children and adolescents. There are currently no standardized second-line treatments for r/r EWS and the prognosis for these patients remains poor. There is an urgent need for new therapeutic strategies that combine novel targeted therapies with new mechanisms of action and existing chemotherapy regimens of established but limited efficacy,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “Elraglusib is one of the few novel targeted agents being pursued for the refractory EWS population and continues to show promise as a viable therapeutic option. Early clinical data suggest that the enhanced antitumor activity of chemotherapy observed in multiple preclinical refractory cancer models is translating well into clinical responses.”
The ongoing Phase 1/2 Trial (NCT 04239092) is an open-label, multicenter study evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including EWS and EWS-related pediatric small round cell sarcomas. To date, the study has enrolled 6 patients with relapsed/refractory EWS (>1 remission); one patient with a desmoplastic small round cell tumor (DSRCT), an ultra-rare, highly aggressive pediatric sarcoma; and one patient with a CIC rearrangement. All patients were treated with elraglusib in combination with cyclophosphamide/topotecan.
Two patients with recurrent /refractory EWS are experiencing ongoing complete responses (CR), two patients achieved stable disease (SD), and two patients withdrew from the study before their tumor response could be assessed (Table 1). The patient with Desmoplastic Small-Round-Cell Tumor (DSRCT) achieved a partial response (PR) with a 52% reduction in tumor size but withdrew from the study and is now being followed for survival.
Table 1. Summary of EWS and other small round cell sarcomas treated in Clinical Study 1902.
| Patient | Tumor Type | Best Overall Response | OS (days)1 |
| 1 | EWS | CR (CT and CMR by PET) |
Alive OS = 933 days |
| 2 | EWS | CR (CMR by PET) | Alive OS = 284 days |
| 3 | DSRCT | PR | Alive OS = 329 days |
| 4 | EWS | SD | OS = 177 days |
| 5 | EWS | SD | OS = 272 days |
| 6 | EWS | Not Determined. Patient withdrew from the Study |
Alive OS = 318 (LTFU) |
| 7 | EWS | Not Determined. Patient withdrew from the Study |
OS = 89 days |
| 8 | CIC-rearrangement | Not Determined. Patient withdrew from the Study |
N/A |
1 As of most recent follow-up visits May – August 2024
“We are pleased to share our continued, promising progress with elraglusib in r/r EWS,” said Dr. Andrew Mazar, Actuate’s Scientific Co-Founder and Chief Operating Officer. “Although the sample size is small, we are encouraged by the disease stabilization and two ongoing complete responses observed, including one patient with an overall survival of over 2.5 years. These results are considered promising by clinical experts in pediatric oncology, particularly given the significant unmet medical need and lack of therapeutic alternatives in recurrent EWS, and support the continued development of elraglusib in this rare cancer patient population.”
The 1902 study remains open only to patients with recurrent EWS, who will be treated with the combination of elraglusib with cyclophosphamide/topotecan. The study will enroll up to 12 total EWS patients to provide additional rationale for moving the elraglusib/cyclophosphamide/topotecan combination into a phase 2 study in patients with recurrent EWS. Actuate plans to meet with the FDA to discuss the design of a phase 2 study and options for accelerating the development path for elraglusib to commercial registration for the treatment of EWS.
About Ewing Sarcoma
Ewing sarcoma (EWS) is a highly metastatic form of sarcoma that ranks as the second most prevalent primary malignant tumor of childhood and adolescence originating in bone with a peak incidence at the age of 15 years. Approximately 25% of new EWS patients have metastatic disease when first diagnosed, which is the most significant predictor of poor survival. Treatment options for relapsed/refractory metastatic EWS are limited. Despite intensive therapy, recurrent EWS, whether local or with distant metastases, is almost always fatal. While the use of chemotherapy regimens in conjunction with surgery has resulted in the 5-year survival rate increasing from 59 to 78% in children and young adolescents, and from 20 to 60% in adults, to date, no standard treatment has been defined in the relapsed/refractory setting.
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 product, elraglusib (a novel GSK-3 inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy including several DDR pathways. For more information on the 1902 Study, please visit ClinicalTrial.gov and reference Identifier NCT04239092.
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