On November 10, the U.S. Food and Drug Administration (FDA) approved pimicotinib (Pimjetmi), a kinase inhibitor, for adults with symptomatic tenosynovial giant cell tumor (TGCT) for whom surgical resection may cause worsening functional limitation or severe morbidity.
MANEUVER Trial
Efficacy was evaluated in MANEUVER (ClinicalTrials.gov identifier NCT05804045), a double-blind, randomized (2:1), placebo-controlled, international trial in patients with TGCT for whom surgical resection may cause dysfunction or serious complications. Eligible patients had a confirmed diagnosis of symptomatic TGCT with measurable disease with at least one lesion having a minimum size of 2 cm. Patients were randomly assigned to receive pimicotinib at 50 mg or placebo once daily. Randomization was stratified by geographic region (China vs non-China).
In MANEUVER, pimicotinib demonstrated a statistically significant improvement in objective response rate at week 25 as assessed by blinded independent review committee based on Response Evaluation Criteria in Solid Tumors version 1.1 compared with placebo (56% vs 3% for placebo; P < .0001). Pimicotinib also demonstrated clinically meaningful and statistically significant improvements as compared to placebo across secondary endpoints relevant to patients’ daily lives, improving relative range of motion (P = .0003), physical functioning (P = .0074), and pain (P < .0001). The MANEUVER study was presented at the 2025 ASCO Annual Meeting (Abstract 11500). In the longer-term follow up (median = 14.3 months for patients initially randomly assigned to pimicotinib) presented at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract 2690MO), the median duration of response was not reached. The majority (77%) of patients with response at 25 weeks maintained clinical benefit after an additional 12 months of follow-up.
The most common (> 20%) adverse reactions were pruritus, rash, face edema, periorbital edema, fatigue, nausea, headache, and peripheral edema. The most common (> 30%) lab abnormalities were increased levels of creatine phosphokinase, lactate dehydrogenase aspartate aminotransferase, lipase, cholesterol, amylase, and alanine aminotransferase.
The prescribing information includes warnings and precautions for hepatotoxicity, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.
“TGCT can profoundly affect patients' daily lives through persistent pain, swelling, and loss of joint function,” said Sydney Stern, PhD, MS, TGCT Support, a Program of the Life Raft Group. “For symptomatic patients who are not likely to benefit from surgery alone, there remains need for treatment options which are tolerable and effectively address the burden of disease, shrink their TGCT, and improve pain and function.”
Recommended Dosage
The recommended pimicotinib dosage is 50 mg orally once daily with or without food.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The European Medicines Agency was an official observer of this review. The applications may be undergoing the submission process or still be under review at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Pimicotinib received Fast Track and Breakthrough Therapy designation.
