CSF1R Inhibition in Patients with Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase I Study of Vimseltinib

Hans Gelderblom, Albiruni A. Razak, Matthew H. Taylor, Todd M. Bauer, Breelyn Wilky, Javier Martin-Broto, Alejandro F. Gonzalez, Piotr Rutkowski, Bartlomiej Szostakowski, Thierry Alcindor, Ramy Saleh, Sofia Genta, Silvia Stacchiotti, Michiel van de Sande, Andrew J. Wagner, Nicholas Bernthal, Lara E. Davis, Jacqueline Vuky, Christopher Tait, Bahar MatinSupraja Narasimhan, Maitreyi G. Sharma, Rodrigo Ruiz-Soto, Matthew L. Sherman, William D. Tap

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3996-4004
Number of pages9
JournalClinical Cancer Research
Volume30
Issue number18
DOIs
StatePublished - Sep 15 2024

ASJC Scopus subject areas

  • General Medicine

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