(P 176) SAFETY, EFFICACY, AND PATIENT-REPORTED OUTCOMES WITH VIMSELTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR WHO RECEIVED NO PRIOR ANTI–COLONY-STIMULATING FACTOR 1 THERAPY: ONGOING PHASE 2 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 recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an investigational, oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Here, we report updated safety, efficacy, and patient-reported outcome (PRO) data from Cohort A of the phase 2 part (expansion) of an ongoing phase 1/2 study (NCT03069469) for patients (pts) with TGCT treated with vimseltinib who did not receive prior specific anti-CSF1/CSF1R agents.

Methods: Pts with TGCT not amenable to surgery and no prior anti-CSF1/CSF1R therapy (previous treatment with imatinib or nilotinib was allowed) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). The primary objectives for Cohort A were to evaluate safety, tolerability, and antitumor activity (by independent radiological review [IRR] using Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]). PROs (secondary objectives) were also evaluated and reported for the 25-week timepoint. Pain was assessed by 2 items from the brief pain inventory (BPI; worst pain and average pain [baseline: average from a 2-week period during screening; week 25: average from weeks 2 and 3 of month 6]) and compared with tumor responses at 25 weeks (by IRR using RECIST v1.1).

Results: As of Jan 27, 2023, 46 pts with TGCT with no prior anti-CSF1/CSF1R therapy were enrolled (enrollment complete; Table). Median age was 44 years (range, 21–71), and the most common tumor location was the knee (57%; 26/46). The safety profile remained consistent with prior reports. Most nonlaboratory treatment-emergent adverse events (TEAEs) were grade 1/2; grade 3/4 TEAEs (≥5% of pts) were elevated creatine phosphokinase and hypertension. There were no treatment-related serious adverse events and no evidence of cholestatic hepatotoxicity. TEAEs led to dose reductions and interruptions in 50% (23/46) and 65% (30/46) of pts, respectively. The median treatment duration was 15.9 months (range, 0.2–24.9; mean, 13.4 months); 52% (24/46) of pts were still on treatment at the time of this analysis. Reasons for treatment discontinuation included adverse events (n=3), physician decision (n=6), and withdrawal by pt (n=13). No pts progressed as assessed by IRR using RECIST v1.1 (median follow-up from first dose, 16.7 months). The objective response rate (ORR) was 60% (27/45; Table 1). The majority of responses (67%; 18/27) were achieved within 6 months after treatment initiation, with a median time to first response of 3.7 months (range, 1.8–22.2). At week 25, 48% (22/46) and 52% (24/46) of pts demonstrated a ≥30% reduction in BPI worst pain and average pain, respectively. Most pts who had a tumor response at week 25 also experienced ≥30% reductions in BPI worst pain and average pain (among responders with BPI data available at week 25; Table 2). Pts with stable disease (SD) at week 25 also experienced ≥30% reductions in BPI worst pain and average pain.

Conclusion: Longer follow-up demonstrated that vimseltinib continued to be well tolerated with a manageable safety profile in pts with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve with a promising overall ORR. At week 25, the majority of responders experienced ≥30% reductions in worst and average pain. Pain reductions were also observed in pts with SD, suggesting that vimseltinib provides pain relief with or without an objective tumor response. Taken together, these data demonstrate that vimseltinib can provide antitumor activity and pain relief in pts with TGCT.