Actuate Therapeutics, Inc. has announced promising results from its ongoing Phase 1/2 clinical trial evaluating elraglusib in patients with relapsed/refractory Ewing Sarcoma (r/r EWS). The trial, an open-label, multicenter study, is assessing the safety and efficacy of elraglusib in combination with cyclophosphamide/topotecan in pediatric patients with relapsed/refractory malignancies, including EWS and EWS-related sarcomas.
The early clinical data revealed two patients with r/r EWS experiencing ongoing complete responses (CR). Furthermore, the data showed approximately 62% disease control rate in the first eight patients. These findings suggest that the enhanced antitumor activity of chemotherapy observed in preclinical refractory cancer models may be translating into clinical benefits.
Elraglusib's Impact on Ewing Sarcoma
Ewing sarcoma is a highly metastatic form of sarcoma and the second most prevalent primary malignant tumor in children and adolescents. According to Actuate Therapeutics, approximately 25% of new EWS patients have metastatic disease at the time of initial diagnosis, which is the most significant predictor of poor survival. The current treatment landscape for r/r EWS lacks standardized second-line treatments, resulting in a poor prognosis for these patients.
Daniel Schmitt, President & Chief Executive Officer of Actuate, emphasized the urgent need for new therapeutic strategies, stating, "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."
Trial Design and Patient Outcomes
The Phase 1/2 trial (NCT 04239092) has enrolled patients with relapsed/refractory EWS (>1 remission), as well as patients with desmoplastic small round cell tumor (DSRCT) and CIC rearrangement. All patients were treated with elraglusib in combination with cyclophosphamide/topotecan.
In addition to the two complete responses, two patients achieved stable disease (SD). One patient with Desmoplastic Small-Round-Cell Tumor (DSRCT) achieved a partial response (PR) with a 52% reduction in tumor size, though the patient later withdrew from the study. The overall survival (OS) data for the patients with complete responses are notable, with one patient alive at 933 days and another at 284 days as of the most recent follow-up visits between May and August 2024.
Future Development Plans
The 1902 study remains open exclusively to patients with recurrent EWS, treated with the elraglusib, cyclophosphamide, and topotecan combination. Actuate plans to enroll up to 12 EWS patients to further support the transition of this combination into a phase 2 study for recurrent EWS. The company intends to engage with the FDA to discuss the design of a phase 2 study and explore options for accelerating elraglusib's development pathway toward commercial registration for EWS treatment.
Dr. Andrew Mazar, Actuate’s Scientific Co-Founder and Chief Operating Officer, commented on the results, stating, "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] support the continued development of elraglusib in this rare cancer patient population."
About Elraglusib
Elraglusib is Actuate's lead investigational drug, a novel GSK-3 inhibitor targeting molecular pathways involved in tumor growth and resistance to conventional cancer drugs. The drug is being explored for its potential to enhance the effectiveness of chemotherapy and address unmet needs in high-impact, difficult-to-treat cancers.
