FGFR wild-type

Although some typical FGFR inhibitor-related side effects were observed, they were manageable and futibatinib had a good safety profile. Futibatinib is an important drug for biliary tract cancer, which has limited treatment options; its development is underway for other types of cancer, and it is expected to benefit more patients.

P2, N=55, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed

Although FGFRalt did not predict outcomes in the overall cohort, for patients treated with 1L ICI, FGFRalt had significantly higher rates of progression than FGFRwt patients. Further validation is needed to determine whether FGFRalt has a decreased benefit from ICI therapy.

This last finding entails that also this setting of patients could benefit from FGFR targeted therapies, widening indication of these drugs for iCCA patients beyond current approval. Future clinical studies are therefore encouraged to confirm this hypothesis.

Tinengotinib has promising clinical benefit for FGFR2 fusion CCA after prior FGFRi and for non-fusion FGFR alterations. Tinengotinib-related toxicities were manageable. An ongoing randomized, controlled phase III study will evaluate the clinical efficacy, safety, and pharmacodynamic effect of Tinengotinib vs Physicians’ choice in subjects with FGFR2-altered refractory/relapsed CCA after prior chemotherapy and FGFRi therapy.

P2, N=55, Active, not recruiting, TransThera Sciences (Nanjing), Inc. | Recruiting --> Active, not recruiting | N=80 --> 55 | Trial completion date: Sep 2023 --> May 2024 | Trial primary completion date: Sep 2023 --> May 2024

FGFR3 mutation can attenuate prognosis and response to ICB in patients with metastatic UC. FGFR3-mutated UC carries a stronger immunosuppressive microenvironment in comparison with FGFR3-wildtype UC. Inhibition of FGFR3 might activate the immune microenvironment, and the combination of FGFR inhibitor targeted therapy and ICB might be a promising therapeutic regimen in metastatic UC, providing important implications for UC clinical management.

For ex vivo drug testing, tumor clusters were isolated, seeded, and exposed to single-agent chemotherapy: carboplatin, cisplatin, gemcitabine and targeted therapy (erdafitinib). A correlation with clinical response to chemotherapy could not be established due to a lack of successfully screened patients with matching clinical chemotherapy treatment. For NMIBC, however, differential ex vivo sensitivity to gemcitabine, and a preliminary correlation for ex vivo erdafitinib sensitivity and FGFR3 mutation status offers a potential solution to select NMIBC patients for effective (novel) treatment options.

Conclusions In our cohort, FGFR3 alterations are neither predictive nor prognostic for 1st-line platinum or 2nd-line IO. Further investigation is needed.

Conclusions There was no statistically significant difference in RW OS between pts with FGFR+ or FGFRadv/ met solid tumors, with a median OS of ∼1 year in both groups. These results highlight the poor prognosis and high unmet need for novel, targeted tx.

To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC.

FIPS effectively predicted survival in BLCA. Patients with different FIPS exhibited diverse immune infiltration and mFGFR3 status. FIPS might be a promising tool for selecting targeted therapy and immunotherapy for patients with BLCA.