Phase 1/2 Trial of Silmitasertib in Sarcoma and Brain Tumors to Proceed

• The FDA has issued a “study may proceed” letter to Senhwa Biosciences regarding the phase 1/2 study (NCT06541262) of silmitasertib (CX-4945) for the treatment of pediatric and adult patients with relapsed/refractory solid tumors.
• The study includes the investigation of the agent in Ewing sarcoma and osteosarcoma.
• Senhwa Biosciences plans to apply for orphan drug designation (ODD) and rare pediatric drug designation (RPDD) for silmitasertib in neuroblastoma.

The phase 1/2 study of silmitasertib in pediatric and adult patients with relapsed/refractory solid tumors, including Ewing sarcoma and osteosarcoma, may proceed with clearance from the FDA.¹

Silmitasertib is a first-in-class, potent, and highly selective casein kinase 2 (CK2) inhibitor. Elevated CK2 activity is seen across multiple cancer types. The agent is administered orally and appears to effectively target CK2 without toxicity.²

In July 2024, the FDA received the investigational new drug application submission for this trial.³ Senwha Biosciences, the sponsor, plans to apply for FDA ODD and RPDD for silmitasertib in neuroblastoma.¹

About the Phase 1/2 Trial of Silmitasertib

The study is evaluating silmitasertib plus chemotherapy for the treatment of pediatric and adult patients with relapsed/refractory solid tumors. There is an estimated enrollment of 114 patients.⁴

The primary end points of phase 1 are incidence of adverse events and dose-limiting toxicities to determine the recommended phase 2 dose (RP2D). For phase 2, the primary end point is overall response rate. Secondary end points including progression-free survival and overall survival.

Phase 1 is evaluating 2 dose levels of silmitasertib, 600 mg/m2 and 800 mg/m2 twice per day. Patients with neuroblastoma also are receiving a chemotherapy regiment of irinotecan and temozolomide, while patients with sarcoma receive vincristine, irinotecan, and temozolomide. In phase 2, patients with Ewing sarcoma and neuroblastoma will receive their respective chemotherapy regimens plus silmitasertib at the RP2D.

Patients must be less than 30 years old at the time of diagnosis and have a confirmed diagnosis of relapsed/refractory neuroblastoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, or liposarcoma for phase 1. In phase 2, only patients with Ewing sarcoma and neuroblastoma will be included. Patients must also have a Lansky or Karnofsky performance score of 50 or higher and adequate organ function at the time of enrollment. Those who are currently receiving investigational drugs, vitamin K antagonists, statins, or other anticancer agents are not eligible for participation.

REFERENCES:

1. Senhwa Biosciences receives US FDA study may proceed letter for the phase I/II study of silmitasertib (CX-4945) in combination with chemotherapy in children and young adults with relapsed refractory solid tumors. News release. Senwha Biosciences, Inc. August 6, 2024. Accessed August 8, 2024. https://tinyurl.com/3pmtacht

2. Products. Senhwa Biosciences, Inc. Accessed August 8, 2024. https://www.senhwabio.com/en/products/CK2

3. 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 August 8, 2024. https://tinyurl.com/4nv5x5ee

4. Silmitasertib (CX-4945) in combination with chemotherapy for relapsed refractory solid tumors. ClinicalTrials.gov. Updated August 7, 2024. Accessed August 8, 2024. https://clinicaltrials.gov/study/NCT06541262