A global study evaluating the combination of silmitasertib plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in the frontline treatment of patients with cholangiocarcinoma (CCA), a rare form of bile duct cancer, has demonstrated promising results. According to Senhwa Biosciences, Inc, the phase 1b/2 trial met its primary endpoint during an interim analysis by demonstrating a statistically significant difference in the silmitasertib plus gemcitabine and cisplatin arm.

The trial’s clinical data were presented during the virtual 2021 American Society of Clinical Oncology GI Cancers Symposium. According to Senhwa Biosciences, the study’s findings indicate a clinically meaningful improvement in progression-free survival (PFS) (P<0.05). Consequently, the trial was stopped early once superior efficacy was confirmed.

"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.

The trial enrolled 88 patients who define the intent-to-treat (ITT) population, of whom 87 patients received silmitasertib in the phase 1b (n=50) and phase 2 (n=37) portions of the study, and were included in the safety population. Additionally, 55 patients were able to complete at least 1 full cycle of therapy, without dosing interruption or dose reductions and form the modified intent-to-treat (mITT) population. The primary efficacy outcome measure was assessed with PFS.

The efficacy findings for silmitasertib compare favorably with those reported in the literature for gemcitabine and cisplatin in the BT22 study that looked at gemcitabine alone verses gemcitabine and cisplatin in combination. Both studies included 6 weekly tumor scans. The phase 1b/2 trial also demonstrated results as follows:
  • Median PFS in the mITT population (11.2 months) is a clinically meaningful improvement compared with the study's phase 2 control group (5.8 months). PFS was approximately 5 months longer than in the BT22 study (5.8 months)
  • Median overall survival in the mITT population (17.4 months) was approximately 6 months longer than in the BT22 study (11.2 months)
  • The overall response rate in the mITT population (32.1%) was higher than in the BT22 study (19.5%).
  • The disease control rate in the mITT population (79.3%) was also higher than that in the BT22 study (68.3%).

Additionally, nearly all patients receiving silmitasertib (99%) in the phase 1b/2 trial experienced at least 1 treatment-emergent adverse events (TEAE), although most were mild or moderate in severity. The most common silmitasertib treatment-related TEAEs were diarrhea (66%), nausea (51%), vomiting (33%), and fatigue (31%).

According to Senhwa Biosciences, the trial’s interim analysis shows that the TEAE profile of silmitasertib compares favorably with that of gemcitabine and cisplatin in the BT22 study, with a lower incidence of hematological adverse events of 21%–39% versus 58.5%–87.8%. Additionally, 66% of patients in the phase 1b/2 trial had a reduction in their CA 19-9 levels.

Based on these trial findings, a randomized phase 3 trial is planned.

Mitesh J. Borad, Li-Yuan Bai, Ming-Huang Chen, et al. Silmitasertib (CX-4945) in Combination with Gemcitabine and Cisplatin as First-Line Treatment for Patients with Locally Advanced or Metastatic Cholangiocarcinoma, a Phase 1b/2 Study. Presented at: ASCO GI Cancers Symposium; virtual. January 17, 2021.