Silmitasertib Drives Disease Control in Advanced Basal Cell Carcinoma

Basal Cell Carcinoma | Maris– stock.adobe.com

Treatment with the novel CK2 inhibitor silmitasertib (CX-4945) led to disease control in patients with locally advanced or metastatic basal cell carcinoma, according to data from a phase 1 trial (NCT03897036) announced by Senhwa Biosciences.1

Data showed that among efficacy-evaluable patients (n = 22), 3 patients achieved a partial response; notably, all responders had locally advanced disease. Ten patients achieved stable disease, including 2 with metastatic disease and 8 with locally advanced disease. The disease control rates were 80% for patients with metastatic disease (n = 4/5) and 65% for those with locally advanced disease (n = 11/17).

Furthermore, the median duration of disease control was 10.3 months for patients with locally advanced basal cell carcinoma and 7.5 months for those with metastatic disease. The median progression-free survival (PFS) was 9.2 months and 3.7 months, respectively. Notably, the median PFS exceeded 21 months in 2 patients.

Regarding safety, adverse effects (AEs) led to treatment discontinuation in 24% of patients, which the company explained compared favorably with other first-line treatment options such as vismodegib (Erivedge) and sonidegib (Odomzo).

“Compared [with] current first- and second-line therapies, [silmitasertib] demonstrated superior tolerability and disease control potential,” Senhwa Biosciences wrote in a news release. “Therefore, Senhwa will actively pursue licensing possibilities while carefully evaluating [silmitasertib’s] potential as a monotherapy or in combination with the second-line immunotherapy [cemiplimab (Libtayo)]. The company aims to explore further indications and potential as a first-line treatment, offering better options for patients.”

CK2 is a multifunctional, serine- and threonine-specific protein kinase that helps regulate various physiological pathways. 2 Studies have shown that CK2 expression is significantly enhanced in multiple tumors. Moreover, clinical data have demonstrated that silmitasertib effectively inhibits the activity of CK2, leading to a reduction in downstream signaling mediated by the protein kinase, including the regulation of different transcription factors involved in tumor progression.

The multicenter, open-label, nonrandomized phase 1 trial enrolled patients at least 18 years of age with basal cell carcinoma.3 Patients were allowed to have histologically confirmed metastatic disease, defined as the presence of measurable distant metastases per RECIST 1.1 criteria; or locally advanced disease, defined as the presence of at least 1 lesion 10 mm or more in at least 1 dimension that was inoperable or contraindicated for surgery. Patients with locally advanced basal cell carcinoma who had a tumor that was not contiguous with the cutaneous disease were enrolled in the metastatic cohort.

Other key inclusion criteria consisted of an ECOG performance status of 0 or 1, and adequate hematopoietic, hepatic, and renal function. Prior treatment with a smoothened inhibitor and disease progression was required for all patients, unless this treatment was intolerable. There was no limit on prior lines of chemotherapy or other systemic therapies; however, prior treatment with hedgehog pathway antagonists was not allowed outside of smoothened inhibitors.

During the dose-escalation portion of the study, silmitasertib was administered at 1000 mg twice per day on days 1 to 28 or days 1 to 21 of each 28-day cycle. In dose expansion, patients were assigned to cohorts based on disease stage (locally advanced vs metastatic) and treatment with the agent at 1000 mg twice per day at the schedule determined in dose escalation.

The study’s primary end point was determination of the recommended phase 2 dose. Secondary end points included the incidence of AEs, objective response rate, the absence of residual basal cell carcinoma in patients with locally advanced disease, and changes in GLI1 expression.

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. April 2, 2025. Accessed April 2, 2025. https://www.senhwabio.com/en/news/20250402
2. Silmitasertib. Senhwa Biosciences. Accessed April 2, 2025. https://www.senhwabio.com/en/products/CK2
3. Treatment duration increment and pharmacodynamic study of CX-4945 in patients with basal cell carcinoma (BCC). ClinicalTrials.gov. Updated April 18, 2023. Accessed April 2, 2025. https://clinicaltrials.gov/study/NCT03897036