(P 116) SAFETY AND EFFICACY OF VIMSELTINIB IN TENOSYNOVIAL GIANT CELL TUMOUR: LONG-TERM PHASE 1 UPDATE

Objective: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and the recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. We report long-term safety and efficacy for patients with TGCT from the phase 1 arm (dose escalation) of the phase 1/2 study (NCT03069469).

Methods: Patients with TGCT not amenable to surgery were treated with vimseltinib. The primary objectives were to determine safety, tolerability, and the recommended phase 2 dose (RP2D).

Results: As of Feb 18, 2022, 32 patients were enrolled (Table); 20 patients remain on study. Overall, only 3 patients discontinued treatment due to an adverse event (AE) or progressive disease. The median treatment duration was 16.4 months. Median age was 51 years (range: 23–73) and the most common location was the knee (63%). Grade 3/4 treatment-emergent AEs in >5% of patients included increases in creatine phosphokinase (CPK), aspartate aminotransferase, lipase, amylase, and hypertension. No postbaseline bilirubin elevations were observed. The combined objective response rate (ORR) was 69% (Table); most responses were achieved within 6 months after initiation of treatment. The RP2D is 30 mg twice weekly (no loading dose).

Conclusion: Vimseltinib demonstrated long-term tolerability in patients with TGCT not amenable to surgery. The ORR continues to improve; sustained responses were observed across all dose cohorts both within and after 6 months, demonstrating continued benefit with prolonged treatment.

Previously presented at ESMO 2022, FPN: Pending, Gelderblom, et al. Reused with permission.

DCR2205117a_CTOS 2022 Vimseltinib Phase 1 Escalation Abstract Encore_TABLE_21Jun2022.docx