Dr Randall on Long-Term Responses and Functional Benefits With Pimicotinib in TGCT

"Patient-centered outcomes, which are critical in studies like this, improved in a clinically meaningful way [with pimicotinib]... much of what we are doing is about quality of life as much as life itself."

R. Lor Randall, MD, FACS, the David Linn Endowed Chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at UC Davis Comprehensive Cancer Center, discussed compelling efficacy and safety data from the phase 3 MANEUVER trial (NCT05804045) evaluating the investigational CSF-1 receptor inhibitor pimicotinib in patients with tenosynovial giant cell tumor (TGCT). TGCT is a locally aggressive and destructive joint tumor driven by the overexpression of colony-stimulating factor 1 (CSF-1), which recruits the macrophages that constitute the bulk of the tumor mass.

Long-term results from MANEUVER, which were presented at the 2025 ESMO Congress, demonstrated that patients who received pimicotinib (n = 63) achieved an overall response rate (ORR) of 76.2% (95% CI 63.8%-86.0%) as assessed by blinded independent review committee (BICR) per RECIST 1.1 criteria. Additionally, the BICR-assessed ORR per tumor volume score (TVS) was 74.6% (95% CI, 62.1%-84.7%). Randall noted that at the week-25 primary analysis, the ORR in the therapeutic arm was 54.0% compared with 3.2% in the placebo group, with a robust and concordant reduction in TVS.

Beyond radiographic success, Randall emphasized the profound importance of patient-centered outcomes in the management of TGCT. Participants in the study experienced clinically meaningful improvements in overall function, including significant reductions in pain and stiffness and enhanced range of motion. These end points are vital in orthopedic oncology, where the preservation of joint function is central to a patient’s quality of life.

From a safety perspective, pimicotinib’s adverse effect profile was manageable and consistent with the CSF-1R inhibitor class, with common toxicities including liver enzyme elevations, edema, and hair color changes, Randall reported. Mechanistically, inhibiting the CSF-1 receptor effectively disrupts the signaling axis and reduces the tumor-associated macrophage burden.

These data supported a new drug application for pimicotinib in TGCT, which was accepted by the FDA on January 13, 2026.

Hear more from Dr Randall about this trial in the following Q&A article.