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. Although benign, 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, particularly in diffuse-type TGCT. 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.

Localized TGCT

U.S. Incidence: ~13,000⁽¹⁾

Disease characteristics include:

• Typically occurs in people 30-50 years old⁽¹⁾

• Genetic translocation causes overproduction of CSF1, triggering migration of inflammatory cells including CSF1R-expressing tumor-associated macrophages (TAMs) to tumor sites⁽²⁾

• Tumors are typically confined to a portion of smaller joints and are more well-defined

Common locations include: fingers, toes, knees, wrists, and ankles

Patient burden includes: pain, joint stiffness, restricted mobility, joint damage, and negative quality of life impact

Diffuse TGCT

U.S. Incidence: ~1,300⁽¹⁾

Disease characteristics:

• Typically occurs in people 30-50 years old⁽¹⁾

• Genetic translocation causes overproduction of CSF1, triggering migration of inflammatory cells including CSF1R-expressing tumor-associated macrophages (TAMs) to tumor sites⁽²⁾

• Tumors typically occur in and around larger joints and are less well-defined

Common locations include: knees, hips, ankles, elbows, and shoulders

Patient burden includes: pain, joint stiffness, restricted mobility, joint damage, and negative quality of life impact

(1) Mastboom et al. Acta Orthopaedica. 2017;88:688-694; (2) West et al. Proc Natl Sci USA. 2006; 103:690-695.

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. At the Connective Tissue Oncology Society (CTOS) Virtual Annual Meeting in November 2020, we announced updated encouraging preliminary results from the ongoing dose escalation portion of the study of vimseltinib in patients with TGCT. Across all cohorts, vimseltinib demonstrated a 41% objective response rate including one complete response (confirmed) and eight partial responses (two confirmed and six to be confirmed at future follow up).

Treatment with vimseltinib was generally well-tolerated in patients with TGCT. Treatment-emergent adverse events (TEAEs) (mostly grade 1/2) occurring in ≥25% of patients regardless of relatedness were blood creatine phosphokinase (CPK) increased (52%), aspartate amino transferase (AST) increased (44%), periorbital edema (44%), fatigue (40%), lipase increased (32%), and alanine aminotransferase (ALT) increased (28%). No serious adverse events (SAEs) related to vimseltinib were reported in the TGCT patients.

The Phase 1/2 study of vimseltinib is ongoing and enrolling into two expansion cohorts, one for TGCT patients with no prior exposure to anti-CSF1/CSF1R agents and a second for patients with prior exposure to anti-CSF1/CSF1R agents. We expect to present updated data from the study in the third quarter of 2021 and are planning to finalize the pivotal development plan in the second half of 2021.

To learn more about this study, click here.

To access most recent data, click here.