Truseltiq (infigratinib)

Notably, combined inhibition of ALKBH5 (using ALKBH5-IN-5) and FGFR1 (using BGJ398/infigratinib) synergistically suppressed ZMIZ1-AS1-driven oncogenesis in vivo. Our study establishes the ALKBH5/ZMIZ1-AS1/PTBP1/FGFR1 signaling axis as a key driver of osteosarcoma progression and a promising target for therapeutic intervention.

P2, N=77, Recruiting, QED Therapeutics, a BridgeBio company | Not yet recruiting --> Recruiting

Advanced CCA remains largely inoperable, and combination gemcitabine plus cisplatin (GemCis) chemotherapy remains the standard treatment for patients affected by this disease...The FDA has approved the targeted therapies ivosidenib, pemigatinib, infigratinib, and futibatinib, as well as the immunotherapy durvalumab, for patients with CCA in recent years...While several promising advancements have been made, further research is required to improve outcomes for patients with CCA. This review provides an up-to-date, comprehensive overview of currently approved targeted therapies in CCA, as well as those under investigation.

Accordingly, inhibition of FGFR activation by TK inhibitors (erdafitinib and infigratinib) or FGF trapping (by NSC12) significantly hampered ACC growth and survival in vitro. Altogether these results demonstrate for the first time the impact of FGF/FGFR blockade on ACC cell growth and survival both in vitro and in vivo. This study may set the rationale to start clinical trials investigating the therapeutic potential of FDA approved FGFR-TK inhibitors for the treatment of aggressive ACC.

P2, N=77, Not yet recruiting, QED Therapeutics, Inc., a Bridgebio company

Effects of the pan-FGFR inhibitor infigratinib (BGJ398) on pediatric cancer cell line viability and migration were evaluated by continuous live cell imaging and compared to FGFR gene expression... Adult and pediatric cancers share common mechanisms of FGFR activation but differ in overall alteration rates and relative abundance of specific aberrations. Preliminary experimental data indicate the therapeutic potential of FGFR inhibitors and suggest mechanisms of resistance in the treatment of pediatric cancers.

MRTKIs regorafenib and infigratinib were used at a concentration of 0.1uM added to the fish water 4 hours post cell inoculation. We have developed an embryonic zebrafish xenograft model of RMS, which allows assessment of tumour growth, vascularisation initiation and therapeutic responses to clinically relevant MRTKIs. The identification of VEGF-A secretion as potential biomarker for Regorafenib response and the separation of therapeutic effects on tumour growth and neovascularisation suggests additional value of our model for response prediction to MRTKIs.

This study shows that combination of CTX and BGJ was most effective against cell lines, highlighting the crucial roles of EGFR and KGFR, with KGFR potentially mediating effects of BGJ. The findings suggest that adding targeted therapies for receptors on relevant cell subpopulations may enhance outcomes in therapy.

This was further confirmed to be efficacious in an ex vivo tumour slice model. Taken together, our results demonstrate the rationale for utilising genomic data to identify drug classes targeting druggable events in low-prevalence cancers and indicate that trametinib alone or in combination with infigratinib should be further explored for clinical UPS management.

A previous study demonstrated the synergistic effect of the allosteric SHP2 inhibitor SHP099 and the FGFR inhibitor BGJ398, suggesting a potential combined targeted therapeutic option for cancer. LC-SF-14 effectively prevented the phosphorylation of FGFR2 and downstream signaling, resulting in tumor regression in vivo. These results indicate that the bifunctional molecule LC-SF-14, the first PTP- and receptor tyrosine kinase (RTK)-targeted dual inhibitor, is a promising lead for the treatment of cancers bearing SHP2 and FGFR oncogenic drivers.

After failure of FGFRi treatment (Lenvatinib and Infigratinib) ten months later, repeated NGS analysis revealed a new gain-of-function mutation in PIK3CA and a homozygous deletion of CDKN2A/B, potentially representing an acquired resistance mechanism. The emerging acquired resistance to FGFR inhibitor treatment has implications for subsequent treatment strategies.

P3, N=6, Recruiting, Kyowa Kirin Co., Ltd.