We demonstrate marked tumor growth inhibition in all FP-RMS PDXs treated with single-agent FGF401 (FGFR4-specific inhibitor) and single-agent lenvatinib (multikinase FGFR inhibitor) and report a clinical response to lenvatinib in a patient with relapsed metastatic FP-RMS. Altogether, we identified new patients with sarcoma who may benefit from FGFR inhibitors, most notably FP-RMS via FGFR4/FGF8 coexpression.

P1/2, N=30, Not yet recruiting, Huahui Health

P1/2, N=30, Nanjing Tianyinshan Hospital; Nanjing Tianyinshan Hospital

While approved pan-FGFR inhibitors provide clinical benefit, their durability is limited by acquired, often polyclonal, on-target resistance mutations affecting key regions of the FGFR2 kinase domain, including the gatekeeper residue (V565), molecular brake residues (N550, E566, K642), and other key variants...Given FGFR2-associated toxicities and the need for subtype selectivity, FGFR4 inhibition was prioritized as a selectivity determinant, while sparing FGFR1 was considered less critical. Guided by structure-based drug design, a reversible aminopyrimidine screening hit was optimized into a novel covalent inhibitor series active against FGFR2 wild-type and clinically relevant resistance mutations. An advanced lead 13 showed favorable potency, ADME properties, and demonstrated proof-of-concept in vivo efficacy in an FGFR2-amplified xenograft model comparable with the standard of care.

We demonstrate marked tumor growth inhibition in all FP-RMS PDXs treated with single agent FGF401 (FGFR4-specific inhibitor) and single agent lenvatinib (multi-kinase FGFR-inhibitor), and report a clinical response to lenvatinib in a relapsed metastatic FP-RMS patient. Altogether, we identified new sarcoma patients who may benefit from FGFR-inhibitors, most notably FP-rhabdomyosarcoma via FGFR4/FGF8 co-expression.

P2, N=33, Recruiting, Asan Medical Center | Not yet recruiting --> Recruiting | Initiation date: Nov 2025 --> Mar 2026

P2, N=118, Enrolling by invitation, Abbisko Therapeutics Co, Ltd | Recruiting --> Enrolling by invitation | N=62 --> 118 | Trial completion date: Oct 2024 --> Dec 2029 | Trial primary completion date: Jul 2024 --> Dec 2028

This method was further successfully applied to a pharmacokinetic study of BPI-43487 capsules in Chinese patients with advanced solid tumors. http://www.chinadrugtrials.org.cn is CTR20210565).

In this study, we designed a series of FGFR4-targeted peptide-radionuclide conjugates (PRCs) based on a high-affinity peptide ligand derived from the binding epitope of the monoclonal antibody U3-1784...In xenograft models, this probe demonstrated high uptake (1.89 ± 0.35% ID/g) and produced high-contrast images specifically in high-FGFR4-expressing tumors. These results indicate that 99mTc-HYNIC-FYQ-8 is a promising peptide-based radiotracer for clinical imaging of FGFR4-overexpressing tumors.

The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.

P2, N=141, Recruiting, Abbisko Therapeutics Co, Ltd

This two-step strategy may represent a novel therapeutic approach for the treatment of therapy-resistant PDAC through senescence induction and subsequent senolysis.