Novel Multikinase Inhibitor Gets Fast Track Status for Cholangiocarcinoma

Bile duct, light micrograph
Bile duct, light micrograph. Microvilli are brown, columnar epithelium is orange. Connective tissue is pink. Two small bile ducts are also seen towards bottom left. Magnification: x100 when printed at 10 centimetres wide.
The designation is based on results from a phase 1 study that evaluated TT-00420 at different dose levels in 9 CCA patients.

The Food and Drug Administration (FDA) has granted Fast Track designation to TT-00420 for the treatment of patients with cholangiocarcinoma (CCA) who have no standard treatment options. The FDA previously granted Orphan Drug designation to TT-00420 for this indication.

TT-00420 is a spectrum selective multikinase inhibitor (Aurora kinases A and B, Janus kinases, fibroblast growth factor receptor [FGFR], vascular endothelial growth factor). The designation is based on results from a phase 1 study ( Identifier: NCT03654547) that evaluated TT-00420 at different dose levels in 9 CCA patients.

Findings showed that 2 patients achieved partial response and 5 achieved stable disease. Among evaluable patients, there were 5 who had FGFR2 fusion or rearrangement and were resistant to treatment with FGFR inhibitors; 1 patients achieved partial response with progression free survival of about 10 months, while the other 4 achieved stable disease. Stable disease and shrinkage of the target lesion was also reported in 1 patient without FGFR alterations.

TransThera is currently investigating TT-00420 in adults with advanced/metastatic and surgically unresectable CCA with: 1) FGFR 2 fusions who failed prior FGFR inhibitor treatment; 2) FGFR2 fusions who responded on prior FGFR inhibitor treatment; 3) with other FGFR alterations; or 4) whose tumors do not contain a detectable FGFR alteration in a phase 2 study ( Identifier: NCT04919642).

The efficacy and safety of TT-00420 is also being evaluated in adults with advanced solid tumors, including CCA, in a phase 1/2 study ( Identifier: NCT04742959). 

“Receiving Fast Track Designation is an important milestone for the development of TT-00420.” said Dr Frank Wu, CEO of TransThera, “We have been and will continue to actively work with FDA, expediting the clinical development of TT-00420 in the CCA field.”

The FDA’s Fast Track designation allows for expedited review of therapies that are meant to treat serious or life-threatening conditions. Generally, the designation is granted to therapies that are expected to have an impact on factors such as survival and daily functioning.


  1. TransThera receives Fast Track designation from FDA for its core product TT-00420 to treat cholangiocarcinoma. News release. TransThera Sciences (Nanjing) Inc. Accessed November 3, 2021.
  2. Piha-Paul SA, Xu B, Janku F, et al. Phase I study of TT-00420, a multiple kinase inhibitor, as a single agent in advanced solid tumors. J Clin Oncol. Published online May 28, 2021. doi: 10.1200/JCO.2021.39.15_suppl.3090.