Pimicotinib Maintains Favorable Safety Profile in Tenosynovial Giant Cell Tumor

Key Clinical Summary: 

• Design/Population: The phase 3 MANEUVER trial evaluated 50 mg of daily pimicotinib among patients with symptomatic, unresectable tenosynovial giant cell tumor. This analysis focused on adverse events of clinical interest during extended follow-up.
• Key Outcomes: The most common adverse events included elevated creatine phosphokinase and edema, with laboratory abnormalities occurring early and resolving relatively quickly. Dose reductions occurred in 25% of patients, and treatment discontinuation due to adverse events occurred in 6%. 
• Clinical Relevance: Pimicotinib demonstrated a manageable safety profile with generally reversible toxicity consistent with CSF-1R inhibitor class effects. These findings support its continued development and potential long-term use in tenosynovial giant cell tumor.

Updated safety results from the phase 3 MANEUVER trial demonstrate that pimicotinib, an investigational CSF-1R inhibitor, was associated with manageable and largely reversible adverse events among patients with symptomatic, unresectable tenosynovial giant cell tumor (TGCT).

These results were presented by Hans Gelderblom, MD, PhD, Leiden University Medical Centre, Leiden, Netherlands, at the 2026 ESMO Sarcoma and Rare Cancers Annual Congress in Lugano, Switzerland. 

In this double-blind trial, 63 patients were randomized to receive either 50 mg of once-daily pimicotinib or placebo for 24 weeks. Following completion, all eligible patients were permitted to enter an open-label extension. Adverse events were monitored through 30 days after the last pimicotinib dose. 

At a median exposure duration of 14.2 months, the most common any-grade adverse events of clinical interest included elevated blood creatine phosphokinase (71%) and edema (62%). Asymptomatic laboratory abnormalities, including elevated blood creatine phosphokinase and elevated aminotransferases, typically occurred early, with median times to onset of 15 days and 17 days, respectively, and resolved relatively quickly. In contrast, clinical adverse events such as edema occurred later, with a median onset of 37 days. 

Other common adverse events of clinical interest included pruritus (60%), rash (54%), periorbital edema (44%), and hypertension (19%). Adverse events led to dose reductions in 25% of patients and treatment discontinuation in 6% of patients.

“This analysis provides insight into the longer-term safety of [pimicotinib], confirming that toxicity was generally manageable, reversible, and consistent with known CSF-1R inhibitor class effect, therefore allowing the potential to maximize treatment benefit in TGCT,” concluded Dr Gelderblom. “Longer-term [pimicotinib] continued to provide sustained, robust antitumor activity with few [adverse event]-related treatment discontinuations.” 

Source: 

Gelderblon H, Ravi V, Stacchiotti S, et al. Manageable longer-term safety with the highly-selective colony stimulating factor-1 receptor (CSF-1R) inhibitor pimicotinib in patients with tenosynovial giant cell tumor (TGCT) in the global MANEUVER trial. Presented at ESMO Sarcoma and Rare Cancers Annual Congress. March 12-14, 2026. Lugano, Switzerland. 289P.