Elraglusib receives FDA orphan drug status for soft tissue sarcomas

This article first appeared with Targeted Oncology™.

The FDA granted orphan drug designation (ODD) to elraglusib for the treatment of patients with soft tissue sarcomas.¹

An open-label, two-tier Phase 2 study is currently evaluating the combination of elraglusib with gemcitabine and docetaxel in patients aged 10 years and older with unresectable or metastatic soft tissue syndrome or bone sarcomas.² In this study, researchers are evaluating the primary endpoint of disease control rate and the secondary endpoint of progression-free survival (PFS).

“We are pleased with the FDA’s ODD, which underscores the potential of elraglusib to address the significant unmet medical need of patients with advanced cancer,” said Daniel Schmitt, MBA, President and CEO of Actuate Therapeutics Inc., in a press release.¹ “Elraglusib is a leading GSK-3β inhibitor that has demonstrated a favorable safety profile and antitumor activity in several solid tumors, including melanoma, Ewing sarcoma, [and] colon and pancreatic cancer. We look forward to the continued development of elraglusib and to working closely with regulators to fulfill its promise for cancer patients.”

Enrollment in the first stratum of the study, stratum A, is open to patients with histologically confirmed, locally advanced, unresectable or metastatic grade 2 or 3 soft tissue sarcoma, including the subtypes undifferentiated pleomorphic sarcoma (malignant fibrous histiocytoma), myxofibrosarcoma, leiomyosarcoma, liposarcoma (excluding well-differentiated), angiosarcoma, synovial sarcoma, rhabdomyosarcoma, spindle cell sarcoma, and high-grade sarcoma not otherwise specified.

The second tier, Tier B, includes patients in whom recurrent/refractory osteosarcoma or Ewing sarcoma is histologically confirmed after first-line therapy.²

All patients must have at least one measurable lesion according to RECIST 1.1, a life expectancy of more than 12 weeks, and adequate organ and bone marrow function. For patients under 16 years of age, a Lansky score of at least 50 is required, and for patients 16 years of age and older, an Eastern Cooperative Oncology Group performance status of 2 or less is required.

Patients in Stratum A with advanced soft tissue syndrome who have received 0 to 3 prior lines of systemic therapy will receive elraglusib at a dose of 15 mg/kg twice weekly in combination with 900 mg/m² Gemcitabine on days 1 and 8 and 75 mg/m² Docetaxel on day 8 of each 21-day cycle until disease progression or unacceptable toxicity. Patients in Stratum B, patients with relapsed/refractory bone sarcoma who have been previously exposed to one or more lines of systemic therapy, will receive an additional 15 mg/kg elraglusib twice weekly plus 900 mg/m² Gemcitabine on days 1 and 8 and 75 mg/m² Docetaxel on day 8 of every 21-day cycle until disease progression or unacceptable toxicity. Investigators will assess patient response every 2 cycles for the first 8 cycles and every 12 weeks thereafter.

About Elraglusib

Elraglusib is a regulator of tumor signaling and the antitumor immune response.³ The active ingredient prevents GSK-3β from acting in cancer cells. Elraglusib has shown efficacy in preclinical studies. Clinical evidence also shows that elraglusib has an antitumor effect in several types of cancer.

The The FDA previously granted the drug ODD approval for the treatment of patients with pancreatic cancer in August 2023.

Elraglusib is also being investigated in another Phase 1 study as monotherapy and in combination with chemotherapy in patients with relapsed/refractory advanced solid tumors or hematologic malignancies.⁴ Here, patients are treated with elraglusib alone in doses of 1 to 15 mg/kg twice weekly (n = 67) or in combination with gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin or pemetrexed/carboplatin (n = 171).

This study has so far shown that the initial recommended Phase 2 dose (RP2D) of elraglusib is 15 mg/kg twice weekly, according to the Clinical cancer research.⁴ This RP2D was later adjusted to 9.3 mg/kg once weekly to reduce central/peripheral vascular access catheter blockages associated with elraglusib treatment.

In part 1, a total of 61 patients were examined for their response. 1 patient with melanoma showed a complete response and 1 patient with acute T-cell leukemia/lymphoma showed a partial response (PR). In part 2, 138 patients were examined for their response and 7 patients showed a PR.

The median PFS was 2.1 months (95% CI, 2–2.6) and the median overall survival was 6.9 months (95% CI, 5.7–8.4).

Further safety findings showed that patients experienced other treatment-emergent adverse events (AEs), including transient visual disturbances and fatigue. In the monotherapy arm, the rate of treatment-emergent AEs of grade 3 or higher was 55.2%. In the combination arm, this rate was 71.3%.

References

1. Actuate Receives FDA Orphan Drug Designation for Elraglusib for Treatment of Soft Tissue Sarcomas. Press release. Actuate Therapeutics, Inc. September 11, 2024. Accessed September 12, 2024. https://www.globenewswire.com/news-release/2024/09/11/2944428/0/en/Actuate-Receives-FDA-Orphan-Drug-Designation-for-Elraglusib-for-Treatment-of-Soft-Tissue-Sarcomas.html

2. A phase 2 study of 9-ING-41 in combination with chemotherapy in adolescents and adults with advanced sarcomas. ClinicalTrials.gov. Updated July 28, 2021. Accessed September 12, 2024. https://clinicaltrials.gov/study/NCT04906876

3. Our Science. Actuate Therapeutics. Retrieved September 12, 2024. https://actuatetherapeutics.com/our-science

4. Carneiro BA, Cavalcante L, Mahalingam D, et al. Phase I study of elraglusib (9-ING-41), a glycogen synthase kinase 3β inhibitor, as monotherapy or in combination with chemotherapy in patients with advanced malignancies. Clinical cancer research. 2024;30(3):522-531. doi:10.1158/1078-0432.CCR-23-1916