(P 173) SAFETY, EFFICACY, AND PATIENT-REPORTED OUTCOMES WITH VIMSELTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR WHO RECEIVED 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 B of the phase 2 part (expansion) of an ongoing phase 1/2 study (NCT03069469) for patients (pts) with TGCT treated with vimseltinib who received prior anti-CSF1/CSF1R therapy.

Methods: Pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy (including pexidartinib, cabiralizumab, or vimseltinib) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). The primary objective was to evaluate the safety and tolerability of vimseltinib. Exploratory objectives for Cohort B included assessing antitumor activity (by independent radiological review [IRR] using Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) and PROs (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, 15 pts with TGCT who received prior anti-CSF1/CSF1R therapy were enrolled (enrollment ongoing). Most pts (80%; 12/15) previously received pexidartinib and discontinued due to progression (n=3), toxicity (n=2), and other (n=7). Median age was 50 years (range, 26–65), and the most common tumor location was the knee (47%; 7/15). The safety profile remained consistent with prior reports. Most nonlaboratory treatment-emergent adverse events (TEAEs) were grade 1/2; grade 3/4 TEAEs in ≥5% of pts were elevated creatine phosphokinase, myalgia, fatigue, arthralgia, eczema, and pain in extremity. There was no evidence of cholestatic hepatotoxicity. One new treatment-related serious adverse event of squamous cell carcinoma of the skin was reported. TEAEs led to dose reductions and interruptions in 27% (4/15) and 60% (9/15) of pts, respectively. Median treatment duration was 7.6 months (range, 0.6–22.1; mean, 10.1 months); 67% (10/15) of pts were still on treatment at the time of this analysis. Reasons for treatment discontinuation included adverse events (n=2), physician decision (n=1), withdrawal by pt (n=1), and other (n=1). No pts progressed as assessed by IRR using RECIST v1.1 (median follow-up from first dose, 8.3 months). The objective response rate (ORR) was 58% (7/12; Table 1). The majority of responses (86%; 6/7) were achieved within 6 months after treatment initiation with a median time to first response of 3.7 months (range, 1.6–8.3). At week 25, 54% (7/13) of pts demonstrated ≥30% reduction in both BPI worst pain and average pain. All pts who had a tumor response at week 25 experienced ≥30% reductions in BPI worst pain and average pain (among responders with BPI data available at week 25; Table 2). Most 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 who received prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve in this pretreated population, with an increased ORR. At week 25, all 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.