What is the mechanism of action of tinengotinib?
Tinengotinib is a multi-kinase inhibitor that has antitumor effects achieved by inhibiting FGFR and VEGFR, the mitotic kinases Aurora A and B, and JAK. Ongoing global clinical trials have shown tinengotinib to be effective across solid tumors, including cholangiocarcinoma, breast cancer, prostate cancer, and liver cancer.
What is the regulatory history for tinengotinib?
Previously, tinengotinib tablets for the treatment of patients with cholangiocarcinoma were included in the NMPA’s list of products for priority review and list of products for breakthrough therapy designation.
Additionally, in 2021, the FDA granted fast track designation to tinengotinib for the treatment of patients with cholangiocarcinoma who have no standard treatment options.2 The regulatory agency has also granted orphan drug designation to the agent for use in those with cholangiocarcinoma.1
Furthermore, in 2024, the European Medicines Agency granted orphan drug designation to tinengotinib for the treatment of patients with biliary tract cancer.3
What data have been most recently seen with tinengotinib tablets in patients with cholangiocarcinoma?
Pooled data from 4 clinical trials investigating tinengotinib tablets in patients with advanced cholangiocarcinoma were presented at the 2025 ESMO Congress.4 This pooled analysis included data from the cholangiocarcinoma cohorts of the following trials:
- A phase 1 trial (NCT03654547) of tinengotinib monotherapy in patients with advanced solid tumors (n = 14)
- A phase 1/2 trial (NCT04742959) of tinengotinib tablets as monotherapy and in combination regimens in patients with advanced solid tumors (n = 27)
- A phase 2 trial (NCT04919642) of tinengotinib in patients with advanced cholangiocarcinoma (n = 55)
- A phase 1/2 trial (NCT05253053) of tinengotinib as monotherapy and as part of combination regimens in patients with advanced solid tumors (n = 14)
Across all trials, patients received tinengotinib tablets administered orally at continuous daily doses ranging from 5 mg to 15 mg or at twice-daily doses of 4 mg or 6 mg until disease progression or unacceptable toxicity. Patients had a median age of 61 years (range, 24-81). Most patients were female (59.1%), White (70.9%), and had an ECOG performance status of 1 (58.2%). FGFR2 alterations were the most common FGFR alterations seen (55.5%) and included FGFR2 fusions or rearrangements (41.8%) and FGFR2 mutations (30.9%).
Among patients with FGFR2-altered cholangiocarcinoma across all dose levels (n = 55), the median progression-free survival (PFS) was 7.26 months (95% CI, 5.55-9.20), and the median overall survival (OS) was 15.93 months (95% CI, 9.43-19.48). Among patients in this subgroup who had received no prior systemic therapy, including no prior FGFR inhibition, and had received tinengotinib at 10 mg daily (n = 35), the median PFS was 6.01 months (95% CI, 4.90-9.10), and the median OS was 17.05 months (95% CI, 8.05-19.48).
Regarding safety, the most common treatment-related adverse effects (TRAEs) seen across the full analysis set (n = 110) were hypertension (any-grade, 55.50%; grade 3/4, 26.40%), diarrhea (42.70%; 5.50%), stomatitis (36.40%; 7.30%), palmar-plantar erythrodysesthesia syndrome (35.50%; 7.30%), increased blood thyroid-stimulating hormone levels (28.20%; 0%), fatigue (24.50%; 4.50%), nausea (23.60%; 0.90%), and decreased appetite (20.90%; 0%). Dose interruptions, reductions, and discontinuations due to treatment-emergent AEs occurred in 72.70%, 32.70%, and 18.20% of patients, respectively. TRAEs led to these respective dose modifications in 56.40%, 28.20%, and 9.10% of patients, respectively.
References
- New drug application for tinengotinib tablets accepted by the National Medical Products Administration. News release. TransThera Sciences Nanjing, Inc. December 19, 2025. Accessed December 19, 2025. https://www.transthera.com/En/Article/detail/id/224.html
- TransThera receives fast track designation from FDA for its core product TT-00420 to treat cholangiocarcinoma. News release. TransThera Sciences Nanjing, Inc. November 3, 2021. Accessed December 19, 2025. https://www.prnewswire.com/news-releases/transthera-receives-fast-track-designation-from-fda-for-its-core-product-tt-00420-to-treat-cholangiocarcinoma-301415291.html
- TransThera announced global phase 3 clinical trial for cholangiocarcinoma authorized in the European Union and orphan drug designation for tinengotinib to treat biliary tract cancer granted by European Medicines Agency. News release. TransThera Sciences, Inc. March 8, 2024. Accessed December 19, 2025. https://www.prnewswire.com/news-releases/transthera-announced-global-phase-3-clinical-trial-for-cholangiocarcinoma-authorized-in-the-european-union-and-orphan-drug-designation-for-tinengotinib-to-treat-biliary-tract-cancer-granted-by-european-medicines-agency-302084086.html
- Javle M, Liao C-YA, Shen L, et al. 81MO Survival and safety of tinengotinib in pooled patients with advanced, fibroblast growth factor receptor (FGFR) inhibitor refractory/relapsed cholangiocarcinoma (CCA). Ann Oncol. 2025;36(suppl 2):S234. doi:10.1016/j.annonc.2025.08.515
