Early Data Show Complete Responses With Elraglusib Combination in Ewing Sarcoma

Andrew Mazar, PhD

Elraglusib (9-ING-41) plus chemotherapy generated preliminary signals of antitumor activity in pediatric patients with relapsed/refractory Ewing and Ewing-related sarcomas, according to findings from a phase 1/2 trial (NCT04239092).¹

Among the patients with recurrent/refractory Ewing sarcoma who received elraglusib plus cyclophosphamide and topotecan (n = 6), 2 have ongoing complete responses (CRs) and have overall survival (OS) durations of 933 and 284 days, respectively; 2 achieved stable disease with respective OS durations of 177 and 272 days; and 2 withdrew from the trial before their tumor responses could be assessed. The 1 patient with desmoplastic small-round-cell tumor enrolled onto the study achieved a partial response with a 52% reduction in tumor size; however, this patient withdrew from the trial and is currently in survival follow-up, with an OS duration of 329 days. One patient with a CIC rearrangement was also enrolled, but withdrew from the trial before tumor response assessment.

“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 relapsed/refractory Ewing sarcoma, 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,” Daniel Schmitt, president and chief executive officer of Actuate, stated in a news release. “Elraglusib is one of the few novel targeted agents being pursued for the refractory Ewing sarcoma 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, open-label, multicenter phase 1/2 trial is investigating the safety and efficacy of elraglusib plus cyclophosphamide and topotecan in pediatric patients younger than 22 years of age with relapsed/refractory malignancies, including Ewing sarcoma and Ewing sarcoma–related pediatric small round cell sarcomas.² Patients need to have either measurable or evaluable disease and a current disease state for which there is no known curative or survival-prolonging therapy with an acceptable quality of life profile. Eligible patients must have a Karnofsky performance level of at least 50% for patients older than 16 years of age or a Lansky performance level of at least 50 for those 16 years of age or younger. Neurologic deficits in patients with central nervous system tumors must be relatively stable for at least 7 days prior to study enrollment, and those who are receiving steroids must be on a stable or decreasing steroid dose for at least 7 days before enrollment. Patients must have received at least 1 frontline treatment regimen for the treatment of their malignancy and have fully recovered from the acute clinically significant toxic effects of this therapy.

All patients are treated in 21-day cycles with twice-weekly elraglusib at an initial dose of 9.3 mg/kg plus cyclophosphamide at 400 mg/m2 on days 1 through 5 and topotecan at 1.2 mg/m2 on days 1 through 5.

The trial plans to enroll a total of 12 patients with Ewing sarcoma to provide additional support for a phase 2 evaluation of the combination in patients with this disease.¹ Actuate plans to meet with the FDA to discuss the design of this phase 2 trial.

“We are pleased to share our continued, promising progress with elraglusib in relapsed/refractory Ewing sarcoma,” Andrew Mazar, PhD, scientific co-founder and chief operating officer of Actuate, added in the news release. “Although the sample size is small, we are encouraged by the disease stabilization and 2 ongoing CRs observed, including 1 patient with an OS 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 Ewing sarcoma, and support the continued development of elraglusib in this rare cancer patient population.”

References

1. 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 September 9, 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/
2. 9-ING-41 in pediatric patients with refractory malignancies. ClinicalTrials.gov. Updated May 16, 2024. Accessed September 9, 2024. https://clinicaltrials.gov/study/NCT04239092