As reported by allsci, China’s National Medical Products Administration (NMPA) has granted conditional approval to TransThera Sciences’ Yochanra (tinengotinib) for adults with unresectable, advanced, or metastatic cholangiocarcinoma (CCA) carrying FGFR2 fusions or rearrangements whose disease has progressed after both systemic treatment and prior FGFR-targeted therapy. The decision establishes the first approved treatment option in China specifically for patients who have exhausted FGFR inhibitor therapy, addressing a significant unmet need in this difficult-to-treat population.
Clinical Data Underpinning the Approval
The authorization is based on results from a pivotal Phase II study conducted across multiple centers in China. The open-label, single-arm trial enrolled 50 patients with advanced cholangiocarcinoma who had previously received chemotherapy as well as at least one FGFR inhibitor.
After a median follow-up of 12 months, independent central review showed an objective response rate of 28%, indicating that more than one-quarter of participants experienced meaningful tumor shrinkage. Responses were durable, with a median duration of response of 8.5 months. Additional outcomes highlighted the drug’s activity in a heavily pretreated population:
- Disease control rate: 82%
- Median progression-free survival: 6.0 months
- Median overall survival: 20.7 months
A randomized Phase III trial comparing tinengotinib with chemotherapy is currently underway in China and is expected to serve as the confirmatory study for the conditional approval.
Designed to Address Resistance Mechanisms
Tinengotinib differs from currently available selective FGFR inhibitors through its multi-targeted mechanism of action. The oral therapy inhibits several kinases, including FGFR1, FGFR2, FGFR3, JAK1/2, VEGFR2, and Aurora A/B.
According to the company, this broader kinase inhibition profile may help overcome resistance mutations that frequently emerge during FGFR-targeted treatment. One example is the FGFR2 V564F mutation, which can limit the effectiveness of more selective FGFR therapies. By targeting additional signaling pathways, tinengotinib is intended to maintain antitumor activity after resistance develops.
Positioning Within the Evolving Cholangiocarcinoma Landscape
The newly approved indication occupies a later-line treatment setting than existing FGFR-directed options. Pemigatinib, which received NMPA approval in 2022, is used for patients with FGFR2-altered cholangiocarcinoma following prior systemic therapy but before progression on an FGFR inhibitor. Tinengotinib therefore fills a treatment gap for patients whose disease advances despite prior FGFR-targeted therapy.
Competition in the FGFR2-positive cholangiocarcinoma space continues to expand. HUTCHMED’s fanregratinib is also seeking regulatory approval in China, while globally, Relay Therapeutics is advancing lirafugratinib, an FGFR2-selective inhibitor developed for patients whose cancers have progressed on earlier FGFR-targeted treatments.
Global Development Continues
Beyond China, tinengotinib has attracted regulatory support in major markets. The therapy has received both Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration for cholangiocarcinoma, as well as Orphan Drug Designation from the European Medicines Agency for biliary tract cancers.
TransThera is also evaluating the compound in other malignancies, with ongoing development plans that include prostate, breast, and liver cancers. The latest approval marks an important milestone for the company and highlights the growing role of precision oncology approaches in cholangiocarcinoma, particularly for patients with molecularly defined disease who have limited treatment options after targeted therapy failure.
