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FDA Grants TT-00420, a Multi-Kinase Inhibitor, Fast-Track Review for Cholangiocarcinoma

Web Exclusives — November 9, 2021

On November 3, 2021, TransThera Sciences announced that the FDA granted its investigational drug, TT-00420, a spectrum-selective multi-kinase inhibitor, a fast-track designation for the treatment of patients with cholangiocarcinoma (CCA) who have no available standard treatment options.1 In preclinical studies, TT-00420 has shown high activity in a variety of FGFR mutations.1

In November 2019, the FDA granted TT-00420 an orphan drug designation for CCA.1 TT-00420 targets cell proliferation, angiogenesis, and immune pathways by inhibiting kinases that are “involved in cytokine signaling and receptor tyrosine kinases (FGFRs and VEGFRs) involved in the tumor microenvironment.”2

The new FDA designation is based on the results of a phase 1, first-in-human dose-escalation clinical trial that evaluated TT-00420 in patients with several advanced or metastatic solid tumors, including triple-negative breast cancer and CCA. The primary end point was dose escalation. Secondary end points were pharmacokinetics and preliminary efficacy.2

As of February 17, 2021, 40 patients were enrolled in dose-escalation cohorts, including 9 patients with CCA, of whom at least 7 patients had ≥1 posttreatment efficacy assessments. Among the evaluable patients with CCA, 5 had an FGFR fusion or rearrangement, as well as resistance to treatment with a previous FGFR inhibitor.

The patients received 1 of 7 doses of TT-00420, including 1 mg, 3 mg, 5 mg, 8 mg, 10 mg, 12 mg, and 15 mg daily. In all, 2 patients with CCA achieved a partial response to TT-00420 therapy that lasted ≥8 months, and 2 patients had stable disease that lasted ≥6 months.1,2 In addition, 1 patient with CCA achieved a partial response within approximately 10 months, and 1 patient who responded to TT-00420 had an 8-month progression-free survival; another patient with CCA but with no FGFR alteration reached stable disease, with a reduction in the tumor size.1,2

“We have been and will continue to actively work with the FDA, expediting the clinical development of TT-00420 in the CCA field,” said Frank Wu, PhD, Chief Executive Officer at TransThera, in the press release.1

TT-00420 has demonstrated high potency in several cancers with FGFR2 mutation. Its molecular profile and mechanism of action facilitate the treatment of patients with heterogeneous tumors, including those who do not have a clear biomarker.

The most common adverse effects of any grade included hypertension (42.5%), diarrhea (25%), vomiting (22.5%), palmar-plantar erythrodysesthesia syndrome (22.5%), and nausea (20%). The most common grade 3 events were hypertension (20%), diarrhea (2.5%), palmar-plantar erythrodysesthesia syndrome (2.5%), and nausea (2.5%).


  1. PR Newswire. TransThera receives fast track designation from FDA for its core product TT-00420 to treat cholangiocarcinoma. November 3, 2021. Accessed November 8, 2021.
  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(15_suppl):Abstract 3090. doi: 10.1200/JCO.2021.39.15_suppl.3090.

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