Vimseltinib: A Precision CSF1R Therapy for Tenosynovial Giant Cell Tumors and Diseases Promoted by Macrophages

Abstract

are employees and shareholders of Deciphera Pharmaceuticals. D.L.F. is founder of Deciphera Pharmaceuticals and a member of its scientific advisory board. S.C.W. is a former employee of Deciphera Pharmaceuticals. B.W. and L.D. are investigators on the clinical study of vimseltinib. B.W. has received financial or material support from GlaxoSmithKline, Lilly, Adaptimmune, Advenchen Laboratories, Daiichi Sankyo, Deciphera, Agenus, and Novartis. B.W. is a paid consultant for Deciphera, Adaptimmune, Springworks, Immune Design, and Daiichi Sankyo and has received research support from Merck Sharp & Dohme, and Agenus. L.D. has received research support from Novartis, Eisai, and BTG. L.D. is a paid consultant for Daiichi Sankyo and Epizyme. Deciphera Pharmaceuticals has patents on vimseltinib.

Long-term follow-up of nilotinib in patients with advanced tenosynovial giant cell tumours

“…Nilotinib's patent expires in 2023 in both the United States and the European Union, and could be a possible solution as a low-cost off-label drug [37]. More recently, new CSF1R inhibitors have been developed and investigated, such as cabiralizumab and vimseltinib [22,38]. Apparently, cabaralizumab is not developed further whereas vimseltinib is currently being explored in a phase III registration study (MOTION) [39].…”

Interactions in CSF1-driven Tenosynovial Giant Cell Tumors

“…These cells attract and stimulate a large population of bystander macrophages (3). A number of studies have shown that these tumors react to inhibition of the CSF1 pathway (6)(7)(8)(9)(10)(11)(12)(13)24). To better understand the "landscaping effect" caused by the neoplastic cells on the tumor micro environment we used scRNA-seq and long read RNA-seq.…”

“…The findings suggested that the chemoattractant and proliferative effect of CSF1 on bystander macrophages could be inhibited by drugs that interfered with the CSF1 pathway. Studies using monoclonal antibodies and small molecule inhibitors for the CSF1 pathway have shown a significant clinical effect (6)(7)(8)(9)(10)(11)(12)(13) and a decrease in tumor size as seen by an imaging measurement specifically designed for TGCT (14). It was hypothesized that the CSF1-expressing neoplastic cells might be activated through an autocrine loop by CSF1R expressed on their surface (3).…”

Targeting Cellular Components of the Tumor Microenvironment in Solid Malignancies

“…Preclinical activity of vimseltinib alone, or in combination with anti-PD1 mAb, was shown, together with Mф depletion and suppression of CSF1R kinase activity. Moreover, in the phase I/II trial (NCT03069469), vimseltinib showed a tolerable safety profile, and biological as well as clinical activity in 13/29 patients [ 36 ].…”