FDA Grants Fast Track Designation to TT-00420 for Cholangiocarcinoma

Patients with cholangiocarcinoma may derive benefit from treatment with TT-00420, which was recently given a fast track designation by the FDA.

The clinical-stage spectrum-selective kinase inhibitor TT-00420 was granted a fast track designation by the FDA for patients with cholangiocarcinoma who have no available standard treatment options, according to a press release from developer TransThera Sciences.1

The designation is based on results from a phase 1 study that assessed TT-00420 at several dose levels in patients with advanced or metastatic solid tumors, including triple-negative breast cancer and cholangiocarcinoma.2 Notably, at least 7 patients received 1 or more post-treatment efficacy assessments. Additionally, 2 patients with cholangiocarcinoma who received 8 mg and 10 mg of the agent, respectively, achieved a partial response (PR). Five other patients had stable disease.

Data from the study helped to support further exploration of TT-00420 in this patient population.

“Receiving fast track designation is an important milestone for the development of TT-00420,” Frank Wu, PhD, chief executive officer at TransThera, said in a press release. “We have been and will continue to actively work with FDA, expediting the clinical development of TT-00420 in CCA field.”

TT-00420 has demonstrated high potency in a variety of FGFR2-mutant diseases in preclinical research. Additionally, its molecular profile and mechanism of action allow for the treatment of heterogeneous tumors, including patients who do not have clear markers.

The phase 1 first-in-human dose escalation and expansion trial included 40 patients who were treated with 1 of 7 doses of TT-00420 at 1 mg, 3 mg, 5 mg, 8 mg, 10 mg, 12 mg, and 15 mg daily.

Among evaluable patients, 5 had an FGFR fusion or rearrangement and resistance to a prior FGFR inhibitor. One patient in the cholangiocarcinoma cohort achieved a PR within approximately 10 months. Additionally, 1 responder had a progression-free survival time of 8 months and another without an FGFR alteration achieved stable disease with a reduction in tumor size.

The most common suspected adverse effects (AEs) at any-grade included hypertension (42.5%), diarrhea (25.0%), vomiting (22.5%), palmar-plantar erythrodysaesthesia syndrome (22.5%), and nausea (20.0%). Additionally, the most common grade 3 AEs were hypertension (20.0%), diarrhea (2.5%), palmar-plantar erythrodysaesthesia syndrome (2.5%), and nausea (2.5%).

TT-00420 was previously granted an orphan drug designation by the FDA in November 2019.


  1. TransThera receives fast track designation from FDA for its core product TT-00420 to treat cholangiocarcinoma. News release. TransThera Sciences. November 3, 2021. Accessed November 3, 2021. https://bit.ly/3nWuiVu
  2. Piha-Paul SAA, 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. 2021;39(suppl 15):3090-3090. doi:10.1200/JCO.2021.39.15_suppl.3090