Data Demonstrate Efficacy of Silmitasertib Plus Gemcitabine and Cisplatin Combination Treatment for Cholangiocarcinoma

Data from a phase 1b/2 trial investigating the treatment of cholangiocarcinoma (CCA) with the combination of silmitasertib plus gemcitabine and cisplatin in comparison with gemcitabine and cisplatin found a statistically significant difference in the silmitasertib plus gemcitabine and cisplatin arm of the study, according to presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI).

The researchers explained that the findings demonstrated a clinically meaningful improvement in progression-free survival (PFS) (P<0.05), allowing them to stop the trial early upon observing the confirmation of the combination treatment’s superior efficacy.

"We are encouraged by the preliminary efficacy evidence demonstrated by silmitasertib in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic CCA. The addition of silmitasertib with gemcitabine and cisplatin fulfills an unmet need for the effective treatment for CCA and could change the standard of care, ultimately saving more lives," said John Soong, MD, FCAP, chief medical officer of Senhwa Biosciences, in a press release.

In total, 88 patients were enrolled as part of the intent-to-treat (ITT) population, of whom 87 patients were included in the safety population, receiving silmitasertib in phase 1b (n=50) and in phase 2 (n=37) of the study.

At least a full cycle of therapy was completed by 55 patients, without any interruption in dosing or need for dose reductions, which allowed these patients to form the modified intent-to-treat (mITT) population.

The measure of the primary efficacy outcome was assessed with PFS, with efficacy findings for silmitasertib comparable to those reported in prior research conducted on gemcitabine and cisplatin in the BT22 study. The BT22 study had included 6-weekly tumor scans and investigated gemcitabine alone verses gemcitabine and cisplatin in combination.

Compared with the BT22 study, the median PFS in the mITT population (11.2 months) showed a clinically meaningful improvement compared with the more recent study's phase 2 control group (5.8 months). Additionally, the PFS was approximately 5 months longer in the current study than in the BT22 study (5.8 months), whereas the median overall survival in the mITT population (17.4 months) was approximately 6 months longer than in the BT22 study (11.2 months).

Furthermore, the overall response rate in the mITT population was 32.1%, which was higher than the BT22 study at 19.5%. In the current study, the disease control rate in the mITT population (79.3%) was also higher than in the BT22 study (68.3%).

In the current study, 99% of patients receiving silmitasertib presented with at least 1 treatment-emergent adverse event (TEAE), but the TEAEs were mild or moderate in severity.

The most common treatment-related TEAEs for patients taking silmitasertib were diarrhea (66%), nausea (51%), vomiting (33%), and fatigue (31%).

Based on this interim analysis, the researchers found that silmitasertib in combination with gemcitabine and cisplatin demonstrated promising preliminary efficacy for the treatment of locally advanced or metastatic CCA. The TEAE profile of silmitasertib was also found to be favorable when compared with the TEAEs of gemcitabine and cisplatin observed in the BT22 study, with a lower incidence of hematological adverse events at 21%—39% versus 58.5%–87.8%, respectively.

Additionally, 66% of patients showed a reduction in their CA 19-9 levels, allowing the researchers to conclude there is a need for a randomized phase 3 trial, which has been planned for the future.

REFERENCE

Senhwa Biosciences Presents Positive Cholangiocarcinoma Data. Taipei, Taiwan: Senhwa Biosciences, Inc; January 15, 2021. https://www.prnewswire.com/news-releases/senhwa-biosciences-presents-positive-cholangiocarcinoma-data-301209103.html. Accessed January 26, 2021.