FDA Receives IND Submission for Phase 1/2 Trial of Silmitasertib in Solid Tumors

• An investigational new drug application for a phase 1/2 trial of silmitasertib (CX-4945) plus chemotherapy in pediatric and young adult patients with relapsed/refractory solid tumors has been submitted to the FDA.
• Silmitasertib is a synthetically derived small molecule and a first-in-class potent and highly selective inhibitor of Casein kinase 2 (CK2).
• The agent shows promise due to its favorable safety, pharmacokinetic, and pharmacodynamic profiles and its ability to synergistically enhance the efficacy of DNA-damaging chemotherapeutic agents.

An investigational new drug application has been submitted to the FDA for the phase 1/2 trial evaluating treatment with silmitasertib plus chemotherapy for pediatric and young adult patients with relapsed/refractory solid tumors.¹

Silmitasertib, a first-in-class potent and highly selective inhibitor for CK2, is a synthetically derived small molecule.² The agent is given as sodium salt in hard gelatin capsule shells with oral administration.

CK2 is a protein kinase that shows elevated activity in a variety of cancer types. CK2 also has a direct role in DNA damage repair which can enable tumor cells to survive damage caused by treatment with chemotherapeutics. It has been shown that inhibitors of DNA repair pathways can increase the efficacy of DNA-damaging chemotherapeutic agents when these are used in combination.

Cancer cell or tumor illustration in high detail for medical education or science background, Generative AI: © LAYHONG - stock.adobe.com

In clinical studies, silmitasertib has shown favorable safety, pharmacokinetic characteristics, and pharmacodynamics responses. Silmitasertib effectively targets CK2 and modulates the expected pathways without exhibiting toxicity. When combined with DNA-damaging agents like gemcitabine and cisplatin, silmitasertib synergistically enhances the efficacy of these anticancer treatments.

Silmitasertib will be evaluated in an investigator-initiated trial conducted by the Penn State Health Children's Hospital and the Beat Childhood Cancer Research Consortium.¹ This group consists of more than 50 children’s hospitals and universities and is based at Penn State College of Medicine.

The trial will be conducted in 2 phases with the first phase looking to determine the safety and dosage of silmitasertib when used for treating pediatric patients with relapsed/refractory solid tumors, and the second phase evaluating its efficacy and potential as a novel treatment option for these patients. Patients in the study will include those with solid tumors, including Ewing sarcoma and osteosarcoma.

According to the press release, the company plans to apply for an orphan drug designation from the FDA, as well as a rare pediatric disease designation for the treatment of patients with neuroblastoma.

REFERENCES:

1. Senhwa Biosciences announces IND submission to US FDA for the phase I/II study of silmitasertib (CX-4945) in children and young adults with relapsed refractory solid tumors. News release. Senhwa Biosciences, Inc. July 11, 2024. Accessed July 15, 2024. https://tinyurl.com/4nv5x5ee

2. Products. Senhwa Biosciences, Inc. Accessed July 15, 2024. https://www.senhwabio.com/en/products/CK2