Vimseltinib

TGCT, previously known as pigmented villonodular synovitis or giant cell tumor of the tendon sheath, is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene leading to overproduction of CSF1. TGCT is typically diagnosed in patients aged 30 to 50 years with a lifetime risk of recurrence and negative impact on quality of life. 

Patients with TGCT experience substantial symptomatic burden including pain and stiffness, impaired physical function, and limited range of motion, which negatively impacts quality of life. Surgery is the standard of care and can be curative for most patients with TGCT; however, disease can recur, and multiple surgeries may be needed, increasing the risk of complication and negative outcomes. There is also a subset of patients who are not amenable to surgery and systemic treatment options are limited. If left untreated TGCT can invade the surrounding soft tissue and joint, and may cause significant disability. When untreated, patients experience pain and range-of-motion limitations, moderate to severe joint deformity, degenerative articular changes, and osteoarthritis; resulting bone destruction can require joint replacement or amputation.

We are currently studying vimseltinib in an international, multicenter, open-label Phase 1/2 study to assess its safety, efficacy, pharmacokinetics, and pharmacodynamics in patients with advanced tumors and TGCT.

Phase 1 is a dose escalation phase to determine the recommended phase 2 dose and the maximum tolerated dose. Phase 2 is an expansion phase to evaluate the safety, tolerability, and preliminary efficacy in two TGCT cohorts. Cohort A includes TGCT patients with no prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib is allowed) and cohort B includes patients with prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib are not eligible).

To learn more about this study, click here.

To access the most recent Phase 2 data, click here.

Vimseltinib is being evaluated in the pivotal Phase 3 MOTION study in patients with TGCT. MOTION is a two-part, randomized, placebo-controlled, double-blind study that aims to evaluate the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery. The study met its primary endpoint of objective response rate (ORR) by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25 in the intent-to-treat (ITT) population.

In addition to meeting the primary endpoint, the study met all six key secondary endpoints, all of which were clinically meaningful. 

To learn more about this study, click here.

We are also currently studying vimseltinib in an international, multicenter, open-label Phase 1/2 study to assess its safety, efficacy, pharmacokinetics, and pharmacodynamics in patients with TGCT. In the ongoing study, vimseltinib was well tolerated, exhibited promising antitumor activity and provided clinically meaningful symptomatic benefits in patients with TGCT not amenable to surgery. 

Phase 1 is a dose escalation phase to determine the recommended phase 2 dose and the maximum tolerated dose. Phase 2 is an expansion phase to evaluate the safety, tolerability, and preliminary efficacy in two TGCT cohorts. Cohort A includes TGCT patients with no prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib is allowed) and cohort B includes patients with prior anti-CSF1/CSF1R (previous therapy with imatinib or nilotinib alone is not eligible).

To learn more about the Phase 1 study, click here. To learn more about the Phase 2 study, click here and here.

To access the most recent Phase 1/2 data, click here.