Novel CK2 Inhibitor Silmitasertib Shows Promise in Advanced BCC

Concept illustration of skin cancer

Two patients with advanced basal cell carcinoma (BCC) treated with silmitasertib (CX-4945), a CK2 inhibitor, demonstrated progression-free survival (PFS) exceeding 21 months in a phase 1, dose-expansion trial (NCT03897036), suggesting the agent may offer superior tolerability in patients with BCC who have relapsed after standard therapies and have no other treatment options.¹

Three patients achieved partial responses (PR), defined by over 30% tumor reduction, and 10 patients experienced stable disease (SD), indicating significant disease control.

The multicenter, open-label, treatment duration increment, expansion trial enrolled 25 patients with locally advanced (n = 20) or metastatic BCC (n = 5), all of whom had relapsed following standard therapies and lacked alternative treatment options. Investigators assessed silmitasertib monotherapy in patients who had failed first-line hedgehog pathway inhibitors, with 27.3% also failing second-line PD-1 inhibitors such as cemiplimab (Libtayo) or pembrolizumab (Keytruda).

The primary end point of the study is to determine the recommended phase 2 dose and schedule of silmitasertib in these patients with locally advanced or metastatic BCC.² Secondary end points consist of establishing the safety and tolerability of silmitasertib, assessing the preliminary evidence of antitumor effects in this patient population, and evaluating the effect of silmitasertib on the hedgehog signaling pathway using qRT-PCR in fresh-frozen tissue from patients with locally advanced BCC.

Additional findings from the study showed that among the 22 patients who were eligible for efficacy analysis, the disease control rates were 80% among patients with metastatic BCC (4 patients with complete/partial response or stable disease) and 65% for patients with locally advanced BCC (11 patients with complete/partial response or stable disease).¹

The median PFS was 9.2 months for those with locally advanced BCC and 3.7 months for patients with metastatic BCC. The median duration of disease control across these arms were 10.3 months and 7.5 months, respectively.

For safety, the discontinuation rate of silmitasertib due to adverse events (AEs) was 24%, and the agent displayed promising antitumor efficacy and disease stabilization potential. This suggests improved tolerability compared with existing first-line treatments like vismodegib (Erivedge) and sonidegib (Odomzo).

Senhwa Biosciences, the sponsor of the trial, now plans to pursue licensing opportunities and explore silmitasertib’s potential as both a monotherapy and in combination with second-line immunotherapies.

References:

1. Senhwa Biosciences announces positive clinical data from phase 1/expansion trial of silmitasertib (CX-4945) in the treatment of basal cell carcinoma. News release. Senhwa Biosciences, Inc. April 2, 2025. Accessed April 2, 2025. https://tinyurl.com/5n9bpz4k

2. Clinical trials. Senhwa Biosciences, Inc. Accessed April 2, 2025. https://www.senhwabio.com/en/trial_groups/CX-4945