TY - JOUR
T1 - CSF1R Inhibition in Patients with Advanced Solid Tumors or Tenosynovial Giant Cell Tumor
T2 - A Phase I Study of Vimseltinib
AU - Gelderblom, Hans
AU - Razak, Albiruni A.
AU - Taylor, Matthew H.
AU - Bauer, Todd M.
AU - Wilky, Breelyn
AU - Martin-Broto, Javier
AU - Gonzalez, Alejandro F.
AU - Rutkowski, Piotr
AU - Szostakowski, Bartlomiej
AU - Alcindor, Thierry
AU - Saleh, Ramy
AU - Genta, Sofia
AU - Stacchiotti, Silvia
AU - van de Sande, Michiel
AU - Wagner, Andrew J.
AU - Bernthal, Nicholas
AU - Davis, Lara E.
AU - Vuky, Jacqueline
AU - Tait, Christopher
AU - Matin, Bahar
AU - Narasimhan, Supraja
AU - Sharma, Maitreyi G.
AU - Ruiz-Soto, Rodrigo
AU - Sherman, Matthew L.
AU - Tap, William D.
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/9/15
Y1 - 2024/9/15
N2 - Purpose: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colonystimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. Patients and Methods: This first-in-human, multicenter, open-label phase I/II study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase II dose, and characterize the pharmacokinetics; exploratory objectives included pharmacodynamics and efficacy. Results: Vimseltinib was well tolerated; the majority of nonlaboratory treatment-emergent adverse events were of grade 1/2 severity. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The recommended phase II dose was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7-46.9), and the objective response rate as assessed by independent radiological review using RECIST version 1.1 was 72%. Conclusions: Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT not amenable to surgery.
AB - Purpose: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colonystimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. Patients and Methods: This first-in-human, multicenter, open-label phase I/II study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase II dose, and characterize the pharmacokinetics; exploratory objectives included pharmacodynamics and efficacy. Results: Vimseltinib was well tolerated; the majority of nonlaboratory treatment-emergent adverse events were of grade 1/2 severity. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The recommended phase II dose was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7-46.9), and the objective response rate as assessed by independent radiological review using RECIST version 1.1 was 72%. Conclusions: Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT not amenable to surgery.
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U2 - 10.1158/1078-0432.CCR-24-0103
DO - 10.1158/1078-0432.CCR-24-0103
M3 - Article
C2 - 38995311
AN - SCOPUS:85204161939
SN - 1078-0432
VL - 30
SP - 3996
EP - 4004
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -