(P 337) OMX-0407 A NOVEL SPECTRUM-SELECTIVE SMALL MOLECULE KINASE INHIBITOR IS ACTIVE IN THE TREATMENT OF ANGIOSARCOMA

Objective: OMX-0407 is an orally available spectrum-selective kinase inhibitor targeting a set of oncology-relevant tyrosine kinases as well as the salt-inducible kinase family. It is currently in early clinical trials for the treatment of a variety of solid tumors. The pharmacological effects of OMX-0407 have been studied across various cancer models. Treatment with OMX-0407 in experimental animals has shown a dose-responsive de-phosphorylation of Src family kinases associated with cell proliferation and cell cycle proteins. This leads to a decrease in tumor cell growth, as evidenced by Ki-67 staining. Additionally, OMX-0407 has been observed to alter the tumor microenvironment in animal models by reducing regulatory T cells within the tumor itself, without impacting the peripheral T cells. Furthermore, in a human angiosarcoma patient-derived xenograft model initially derived from a 9-year-old female with an epithelioid angiosarcoma, treatment with OMX-0407 achieved long standing tumour regression.

Methods: At the time of writing a total of 19 patients have received continuous treatment with OMX-0407 administered twice daily in 28-day cycles in a dose escalation study at the following dose levels 10, 30, 60, 90 and 140 mg BD. Subjects were required to have previously treated unresectable solid tumors.

Results: Treatment was well tolerated with the main safety finding being gastro-intestinal adverse reactions. A single dose limiting toxicity – facial swelling secondary to drug allergy was recorded at a dose of 90 mg BD. Treatment with OMX-0407 was associated with reduced phosphorylation of selected Src family kinases in peripheral blood mononuclear cells and a trend towards increased Ki-67 as a proliferation marker was seen in circulating, cytotoxic T cells. One patient with secondary radiation-induced metastatic cutaneous angiosarcoma was treated at doses of up to 60 mg BD and achieved a complete response which is ongoing at nine months. The patient had received previous chemotherapy with paclitaxel and doxorubicin.

Conclusion: OMX-0407 is a promising new agent for the treatment of angiosarcoma. A Phase II study of OMX-0407 in patients who have received at least one previous line of treatment for unresectable angiosarcoma will open for recruitment in the third quarter of 2024. 
The clinical trial is registered as NCT05826600.