Longer-term safety of pimicotinib in tenosynovial giant cell tumor (TGCT): Integrated analysis of phase 1 and phase 3 MANEUVER trial data.

11568 Background: TGCT is a rare, locally-aggressive neoplasm associated with significant morbidity and functional impairment. Colony-stimulating factor-1 receptor (CSF-1R) inhibitors are effective for unresectable TGCT, but current options may be limited by their long-term safety and tolerability. In the Phase 3 MANEUVER trial, pimicotinib (pimi), a highly-selective CSF-1R inhibitor, demonstrated robust tumor responses, clinically meaningful symptomatic and functional improvements, and a tolerable safety profile. This integrated analysis evaluated the longer-term safety of pimi from Phase 1 and 3 trials. Methods: Data for adult patients (pts) with TGCT treated with pimi 50 mg once daily from Phase 1 (NCT04192344, cut-off Dec 31, 2024) and Phase 3 (NCT05804045; MANEUVER, cut-off Mar 12, 2025) trials were pooled for an integrated safety analysis. The open-label Phase 1 study assessed safety, tolerability, and pharmacokinetics of pimi in advanced solid tumors. MANEUVER evaluated efficacy and safety of pimi in unresectable TGCT across a 24-week, double-blind, placebo-controlled phase; a 24-week open-label pimi treatment phase; and an ongoing long-term extension. All treatment-emergent adverse events (TEAEs) and adverse events of clinical interest (AECI) were analyzed and reported as frequencies. Results: In total, 158 pts were included; 65.8% were female and median age was 40.0 (range 18–76) years. Median pimi exposure was 385.5 days; 12.7% of pts had prior exposure to systemic therapy. TEAEs of any grade were reported by 99.4% of pts (Table); most pts reported a maximum grade of 1 (8.9%; n=14/158) or 2 (53.2%; n=84/158). The most reported AECI of any grade by pts were blood creatine phosphokinase (CPK) elevation (72.2%), aminotransferase elevation (59.5%), edema (excluding periorbital edema [POE]) (54.4%), rash (46.2%) and pruritus (43.0%); 20.9% reported fatigue. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The most common AECI leading to dose reduction were rash (5.1%) and edema (excluding POE) (3.2%); for dose interruption, blood CPK elevation (13.9%) and rash (13.3%) were most common. Most AECI resolved/improved following dose reduction or interruption. Treatment discontinuation due to AECI was rare (face edema, 0.6%; rash, 0.6%). Concomitant medication was most commonly used for rash (n=38/73), pruritus (n=31/68), and edema (n=22/86). Conclusions: Pimi showed sustained tolerability with no new safety signals, confirming a favorable safety profile in Phase 1 and 3 trials during extended treatment of >1 year in a larger TGCT population. Clinical trial information: NCT04192344 ; NCT05804045 . Summary of TEAEs. TEAE Pts(N=158)n (%) Any 157 (99.4) Grade ≥3 59 (37.3) Serious 17 (10.8) DR serious 1 (0.6) Leading to dose reduction 33 (20.9) Leading to dose interruption 95 (60.1) Leading to discontinuation 8 (5.1) Resulting in death 1 (0.6) DR resulting in death 0 DR, drug related.