Adverse events and their management in patients with tenosynovial giant cell tumor (TGCT) treated with pimicotinib, after longer-term follow-up from the global phase 3 MANEUVER trial.

Abstract

11571 Background: TGCT is a rare, locally aggressive, soft-tissue tumor associated with significant morbidity. Pimicotinib (pimi) is an oral, highly selective, small molecule colony-stimulating factor-1 receptor (CSF-1R) inhibitor. In the Phase 3 MANEUVER trial (NCT05804045), the primary and key secondary endpoints were met; pimi demonstrated robust tumor responses and symptomatic and functional improvements, with a tolerable safety profile. Here, we report the longer-term safety profile and adverse event management strategies with at least one year of pimi treatment. Methods: Adults patients (pts) with symptomatic unresectable TGCT were randomized (2:1) to pimi 50 mg once daily or placebo for 24 weeks (Part 1), followed by open-label pimi for an additional 24 weeks (Part 2) and an extension phase. Treatment-emergent adverse events (TEAEs) were monitored for 30 days after the last dose and graded using the Common Terminology Criteria for Adverse Events, version 5.0. Results: In total, 63 pts received pimi (median follow-up: 14.3 months). The most frequent laboratory abnormality TEAE was increased creatinine phosphokinase (CPK; 71.4%) and the most common clinical TEAE was pruritus (60.3%). Fatigue occurred in 28.6% of pts. Most TEAEs were Grade 1–2 (Table). Grade ≥3 TEAEs occurred in 46.0% of pts, primarily elevated CPK (15.9%) and rash (6.3%), with no Grade ≥3 periorbital or facial edema observed. TEAEs were managed with dose interruptions (66.7%; median 11 days) and reductions (25.4%), maintaining a high median percentage intended dose (88.2%). Discontinuations were infrequent (6.3%). Concomitant medications were commonly used for AE management; local corticosteroids and antihistamines for rash and pruritus, and diuretics for edema. Conclusions: This analysis confirmed the distinct and manageable safety profile of pimi. Most TEAEs were low grade and managed through dose modifications and standard concomitant medications, enabling sustained dosing and minimal discontinuations. These findings support the longer-term tolerability of pimi in TGCT. Clinical trial information: NCT05804045 . Grades of most common TEAEs (≥30%) in patients treated with pimi in the MANEUVER phase 3 trial. TEAEs, n (%) a Any grade Grade 1 Grade 2 Grade ≥3 Blood CPK increased b Blood LDH increased b AST increased b Amylase increased b 45 (71.4)36 (57.1)35 (55.6)24 (38.1) 20 (31.7)35 (55.6)33 (52.4)16 (25.4) 15 (23.8)1 (1.6)2 (3.2)8 (12.7) 10 (15.9) c 000 Pruritus d Face edema d Rash d Periorbital edema d 38 (60.3)31 (49.2)24 (38.1)23 (36.5) 26 (41.3)22 (34.9)18 (28.6)18 (28.6) 10 (15.9)9 (14.3)2 (3.2)5 (7.9) 2 (3.2)04 (6.3)0 a TEAEs were not mutually exclusive; patients may have had more than one TEAE. b Asymptomatic laboratory abnormalities. c Included one patient with Grade 4 event. d Clinical adverse events. LDH, lactate dehydrogenase; AST, aspartate aminotransferase.