Senhwa Biosciences has commenced a Phase 1/2 clinical trial to evaluate silmitasertib (CX-4945) in pediatric patients with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. The study, involving 114 children and young adults across the US, aims to assess the safety and efficacy of this first-in-class casein kinase 2 (CK2) inhibitor in treating these difficult-to-treat cancers.
Silmitasertib: A CK2 Inhibitor
Silmitasertib, originally developed by Cylene Pharmaceuticals, is a small molecule inhibitor targeting CK2, an enzyme overexpressed in various tumors. Preclinical studies have indicated that silmitasertib exhibits promising anticancer activity, inducing autophagy and promoting apoptosis in cancer cells, particularly in pancreatic, lung, and colorectal cancers. The drug has demonstrated good oral bioavailability and tumor growth inhibition in animal models with good tolerability.
Trial Design and Objectives
The Phase 1/2 trial will assess silmitasertib as a monotherapy and in combination with DNA-damaging chemotherapy drugs like gemcitabine and cisplatin. The primary endpoints include evaluating the safety and determining the recommended Phase 2 dose. Secondary endpoints will focus on assessing the drug's efficacy in terms of objective response rate, duration of response, and progression-free survival.
Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, emphasized the importance of this research, stating, "The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally."
Broader Applications: COVID-19
In addition to its potential in cancer therapy, silmitasertib is also under investigation for treating severe COVID-19. CK2 is implicated in regulating signaling pathways critical for innate immune responses. By inhibiting CK2, silmitasertib may help mitigate the excessive cytokine storm observed in severe COVID-19 cases. Phase 2 results have shown significantly better recovery times for COVID-19 patients treated with silmitasertib compared to standard care, with a favorable safety profile. Studies suggest that silmitasertib and other kinase inhibitors can reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, which are elevated in hospitalized COVID-19 patients.
