Pimicotinib Shows Early, Strong Tumor Response in Tenosynovial Giant Cell Tumors

A phase 3 study found that pimicotinib — an oral, once-daily tyrosine kinase inhibitor — produced rapid and clinically meaningful tumor reduction in adult patients with unresectable tenosynovial giant cell tumors (TGCTs), improving pain, stiffness and physical function.

The MANEUVER trial was conducted at 40 sites across Asia, Europe and North America to evaluate pimicotinib in adults with TGCTs who could not have surgery. The study was led by researchers at Beijing Ji Shui Tan Hospital in China and included a diverse group of patients to better understand how the drug works in real-world settings.

How well does pimicotinib shrink tumors and improve symptoms?

In the study, findings from which were published in The Lancet, more than half of the patients taking pimicotinib saw their tumors shrink significantly. By week 25, 54% of patients on pimicotinib (34 of 63) had a measurable tumor response compared with just 3% (one of 31) of patients taking a placebo. This difference of 51% was statistically significant and the effect was seen across different groups of patients.

Patients on pimicotinib also noticed improvements in symptoms that affect daily life. They reported better range of motion, less stiffness and pain, and improved ability to do everyday activities. These benefits were especially meaningful for patients who are socially or professionally active, or for those whose tumors could not be treated with surgery.

MANEUVER Study Design and Patient Eligibility

MANEUVER was a randomized, double-blind, placebo-controlled study. Between April 27, 2023 and March 29, 2024, 126 patients were screened, and 94 were enrolled. Patients were randomly assigned to receive oral pimicotinib 50 milligrams (mg) once daily (63 patients) or placebo (31 patients) for 24 weeks. Randomization was stratified by region (China versus non-China) and masking was maintained with a placebo identical in appearance to pimicotinib.

Patients completing the first 24 weeks could enter an open-label extension: those on pimicotinib continued the same dosage, while placebo patients could cross over to receive pimicotinib for 24 weeks. Eligible patients were then allowed to continue long-term treatment with pimicotinib.

Safety and Side Effects

Pimicotinib was generally well tolerated. Most treatment-emergent side effects were mild and manageable, including pruritus, facial edema, rash, periorbital edema and fatigue. The only grade 3 (severe) or 4 (life-threatening) side effect occurring in more than 10% of patients was an increase in blood creatine phosphokinase in eight of 63 patients (13%). Dose reductions occurred in 8% of patients and 2% discontinued treatment.

Importantly, no cases of cholestatic hepatotoxicity, drug-induced liver injury, or hair and skin hypopigmentation were reported, addressing safety concerns observed with earlier CSF-1R inhibitors.

What This Means for Patients

Tenosynovial giant cell tumor is a locally aggressive tumor of the joint synovium, bursae or tendon sheaths. Although rare and not life-threatening, it can cause significant pain, stiffness and joint damage. Surgery has been the main treatment but carries risks of complications, delayed recovery and recurrence.

The results of MANEUVER suggest that pimicotinib provides a convenient oral treatment option for patients with unresectable TGCT, reducing tumor burden while improving symptoms and quality of life. Patients may experience earlier relief from stiffness and pain and gain improved mobility and function, particularly when surgery is not feasible.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

“Pimicotinib versus placebo for tenosynovial giant cell tumour (MANEUVER): an international, randomised, placebo-controlled, phase 3 trial” by Dr. Hairon Xu, et al., The Lancet.

“Pimicotinib: a new agent for an orphan disease” by Jean-Yves Blay, The Lancet.

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