Vimseltinib

TGCT is a rare disease caused by a genetic translocation in the colony-stimulating factor 1 (CSF1) gene resulting in overproduction of CSF1, triggering migration of inflammatory cells including CSF1R-expressing tumor-associated macrophages (TAMs) to tumor sites. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. These tumors can grow and cause damage to surrounding tissues and structures inducing pain, joint stiffness, restricted mobility, joint damage, and negative quality of life impact swelling. Surgery is the main treatment option; however, these tumors tend to recur. If untreated, or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability.

Due to the slow-growing nature of TGCT and symptoms similar to other conditions such as sports injuries and arthritis, patients may have a longer path to diagnosis. Patients may visit multiple doctors before receiving a definite diagnosis and treatment plan. Once properly diagnosed with TGCT, patients are referred to an orthopedic oncologist and medical oncologist specializing in sarcomas, especially if they have diffuse disease.

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.

We plan to advance vimseltinib into a pivotal Phase 3 study in patients with TGCT. The MOTION study is two-part, randomized, double-blind, placebo-controlled study of vimseltinib to assess the efficacy and safety in patients with symptomatic TGCT who are not amenable to surgery. In Part 1 of the study, eligible study participants will be assigned 2:1 to receive either vimseltinib or matching placebo for 24 weeks. Participants assigned to placebo in Part 1 will have the option to receive vimseltinib for Part 2 of the study. Part 2 is a long-term treatment phase in which all participants receive open-label vimseltinib. The primary endpoint of the study is ORR at 25 weeks as measured by RECIST v1.1 by blinded independent central review.

To learn more about this study, click here.