OMX-0407: A novel spectrum-selective small molecule kinase inhibitor in advanced/metastatic solid tumors.

3103 Background: OMX-0407 is an orally available spectrum-selective kinase inhibitor that targets key oncology-relevant tyrosine kinases and salt-inducible kinases and is being developed as a first-in-class treatment for solid tumor indications. Preclinical investigations indicate a dual mode of action by sensitizing tumor cells to immune cell induced apoptotic cell death as well as direct inhibition of tumor growth promoting kinases. Methods: This is a phase Ia/Ib dose escalation and expansion study of OMX-0407 (NCT05826600). Eligible patients for the phase Ia dose escalation part had advanced solid tumors and exhausted available therapies. Results: As of the 30 th of October 2024, 24 patients have been treated at dose levels 10 through 140 mg p. o. BID and the phase Ia part has been completed. Solid tumor histologies included melanoma, non-small cell lung cancer, sarcoma and colorectal cancer. OMX-0407 was generally well tolerated, adverse reactions were mainly gastrointestinal. Two dose limiting toxicities were observed: One case of facial swelling secondary to drug allergy at the 90 mg BID dose, and one case of fatigue at the 140 mg BID dose. One durable complete response in a patient with cutaneous angiosarcoma secondary to radiotherapy, resistant to two prior lines of chemotherapy treatment, was observed at 30 mg BID which is ongoing at 16 months (at the time of data cutoff). Pharmacodynamic analyses demonstrated phosphorylation inhibition of target kinases. A recommended phase II dose of 100 mg BID was identified. Conclusions: OMX-0407 has been well tolerated at pharmacologically and therapeutically active dose levels. One very durable response has been observed in an angiosarcoma patient at a low dose level. The phase Ib expansion part at the recommended phase II dose is currently recruiting patients with angiosarcoma and clear cell renal cell carcinoma. Clinical trial information: NCT05826600 .