Silmitasertib plus gemcitabine and cisplatin seems to be effective for the first-line treatment of locally advanced and metastatic cholangiocarcinoma, according to results from a phase 1b/2 clinical trial published in the journal Hepatology

In the phase 2 portion of the study, 55 patients were given 1000 mg of silmitasertib twice a day for 10 days together with gemcitabine and cisplatin on days 1 and 8 of a 21-day cycle, while 29 patients were given only gemcitabine and cisplatin.

The results showed that median progression-free survival was 11.2 months in patients who received silmitasertib with gemcitabine and cisplatin, compared to 5.8 months in patients receiving the chemotherapy alone. The 10-month progression-free survival rate was 56.1% for patients receiving silmitasertib plus gemcitabine and cisplatin and only 22.2% for those receiving gemcitabine and cisplatin alone.


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The median overall survival of patients given silmitasertib was 17.4 months, while that of patients given chemotherapy alone was 14.9 months. 

The overall response rate of patients receiving silmitasertib plus gemcitabine and cisplatin was 34%, and the disease control rate of the triple combination treatment was 86%. The overall response rate of patients receiving only gemcitabine and cisplatin was 30.8%, but the disease control rate of the chemotherapy agents alone was greater than with added silmitasertib at 88.5%.

In terms of treatment-emergent adverse events, 99% of patients given the triple combination treatment and 93% of those receiving chemotherapy alone reported at least 1 treatment-emergent adverse event, the most common of which were diarrhea, nausea, fatigue, vomiting, and anemia. Fatigue affected patients in both treatment groups equally, with 47% of them reporting this adverse event. The other adverse events affected a larger proportion of patients who were given silmitasertib on top of the chemotherapy. A total of 12 patients (10%) discontinued treatment due to treatment-emergent adverse events.

Silmitasertib, an oral small molecule casein kinase 2 inhibitor, is being developed as a potential treatment for cancer and infectious disease.

Reference

Borad MJ, Bai LY, Richards D, et al. Silmitasertib plus gemcitabine and cisplatin first-line therapy in locally advanced/metastatic cholangiocarcinoma: a phase 1b/2 study. Hepatology. Published online September 24, 2022. doi:10.1002/hep.32804