Effect of pimicotinib on tumor response and physical function (PF) by tumor location in patients with tenosynovial giant cell tumor (TGCT): Results from the phase 3 MANEUVER trial.

11567 Background: TGCT is a rare, locally-aggressive, soft-tissue tumor driven by colony-stimulating factor-1 (CSF-1) overproduction, often leading to impaired PF. Pimicotinib (pimi), an oral, highly-selective CSF-1 receptor inhibitor, demonstrated robust tumor responses, clinically meaningful symptomatic and functional improvements, and a tolerable safety profile in patients (pts) with TGCT in the global Phase 3 MANEUVER trial (NCT05804045). Here, we report the effects of pimi on tumor response and PF in joints most commonly affected by TGCT. Methods: In MANEUVER, symptomatic adult pts with unresectable TGCT were randomized 2:1 to once-daily pimi 50 mg or placebo for 24 weeks (Part 1). After Part 1, eligible pts received open-label pimi for 24 weeks (Part 2), followed by an ongoing long-term extension period (Part 3). Longer-term objective response rate (ORR) by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Range of Motion (ROM) responses, and Patient-Reported Outcomes Measurement Information System-PF (PROMIS-PF) scores from Part 1 to Part 3, up to data cut-off, are reported by tumor location for pts randomized to pimi in Part 1. Results: At baseline, 63 pts were randomized to pimi; 71.4% were female and median age was 41.0 years (range 18–69). Median follow-up was 14.3 months and median treatment duration was 14.2 months. Most pts had diffuse TGCT (84.1%), with an affected lower extremity (85.7%), particularly the knee (52.4%). Tumor responses to pimi were comparable for localized (n=8) and diffuse (n=53) TGCT based on ORR by BIRC per RECIST v1.1 (95% CI): 87.5% (47.3, 99.7) vs 75.5% (61.7, 86.2), respectively. ORRs (95% CI) were comparable for pts with lower extremity (n=54) tumors and upper extremity (n=9) tumors: 75.9% (62.4, 86.5) vs 77.8% (40.0, 97.2), respectively, and for knee tumors (n=33) vs other (n=30) locations: 75.8% (57.7, 88.9) vs 76.7% (57.7, 90.1), respectively. Knee ROM improved from baseline to Week 49 (mean change: 8.9 [SD 8.4]). PROMIS-PF scores for lower extremity measures such as walking, climbing stairs, standing, and bending/kneeling improved from baseline (n=54) to Week 49 (n=43) (Table). Conclusions: Pimi provided sustained, clinically meaningful benefits in pts with TGCT, including durable tumor shrinkage and improved ROM and PF, regardless of tumor location. These results support pimi as an effective treatment option for patients with unresectable TGCT. Clinical trial information: NCT05804045 . Longer-term PROMIS-PF scores per item from baseline to week 49. PROMIS-PF score a Mean (SD) Baseline(N=54) Week 49 (N=43) Walk for ≥15 minutes 3.9 (1.0) 4.6 (0.6) Climb stairs 3.3 (1.1) 4.2 (0.8) Stand for 1 hour 2.9 (1.2) 3.7 (1.3) Bend, kneel, or stoop 2.7 (1.3) 3.6 (1.2) a 1-Unable to do; 2-With much difficulty; 3-With some difficulty; 4-With a little difficulty; 5-Without any difficulty.