Tenosynovial Giant Cell Tumor

P=N/A, N=30, Not yet recruiting, Nantes University Hospital

P2, N=20, Not yet recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Although representing just 5% of all identified factors, these appeared in 69% of the included studies, highlighting their prominence in the literature. Apart from the well-known osteoclastogenesis factor CSF1, inflammatory cytokines (TNF-α and IL-1β) and monocyte-macrophage lineage makers (CD68, CD163) are signalling pathways key to TGCT disease progression and associated bone destruction.

P3, N=123, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jul 2026 --> Jul 2028

P3, N=128, Active, not recruiting, SynOx Therapeutics Limited | Trial primary completion date: Apr 2026 --> Dec 2025

The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a least one Lipinski rule of five violation.

Furthermore, there is an absence of severe toxicities that have arisen with other agents in the TGCT treatment space, specifically liver failure. Vimseltinib is a favorable option for patients with TGCTs and further efforts to determine its place in the sequence of overall management are needed.

The results of in vitro-in vivo extrapolation (IVIVE) indicated that coadministration of pexidartinib at a clinically approved dose (400 mg twice daily) with the drugs primarily cleared by UGT1A1, UGT1A6, UGT1A7, UGT1A9, and UGT2B15 would result in a higher risk of DDI. In summary, our results provide useful information for the mechanism underlying pexidartinib-induced hepatotoxicity and clinical safe medication of pexidartinib.

P4, N=40, Recruiting, Shanghai Jiao Tong University Affiliated Sixth People's Hospital | Not yet recruiting --> Recruiting

P4, N=40, Not yet recruiting, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

This study opens promising avenues for developing targeted therapeutic strategies aimed at inhibiting the invasive and osteoclastogenic functions of CD90+PDPN+ FLSs in PVNS. Future research should focus on validating these cells as potential therapeutic targets, possibly through the use of selective inhibitors, which could help mitigate synovial hyperplasia and bone destruction in affected patients.

P=N/A, N=40, Not yet recruiting, Shanghai JiaoTong university Affiliated Sixth People‘s Hospital; Shanghai Jiao Tong University Affiliated Sixth People's Hospital