The U.S. Food and Drug Administration (FDA) has approved pimicotinib (PIMJETMI), a once-daily oral targeted therapy, for adults with symptomatic tenosynovial giant cell tumor (TGCT) when surgical removal could worsen functional limitations or cause severe morbidity.
Announced by Merck on November 10, 2026, the approval introduces another systemic treatment option for patients living with this rare, locally aggressive tumor, which can cause persistent pain, swelling, joint damage, and reduced mobility.
The decision is supported by results from the global Phase 3 MANEUVER trial, which demonstrated significantly higher tumor response rates with pimicotinib compared with placebo, alongside improvements in pain, physical function, and joint mobility.
Why Tenosynovial Giant Cell Tumor Needs More Treatment Options
Tenosynovial giant cell tumor is a rare neoplasm that develops in and around joints, most commonly affecting the knee. Although it rarely metastasizes, TGCT can grow aggressively within affected tissues, potentially causing chronic pain, stiffness, swelling, and progressive destruction of joints and surrounding structures.
The disease often affects young and otherwise healthy adults, making its impact on mobility, employment, and everyday activities particularly significant.
Surgery has traditionally been the mainstay of treatment. However, complete resection is not always possible, particularly in diffuse TGCT, where tumors may involve extensive areas of the joint. Repeated surgery can also increase the risk of complications and lasting functional impairment.
For patients in whom surgery is unlikely to provide sufficient benefit, effective systemic therapies can offer an important alternative.
MANEUVER Trial: The Evidence Behind Pimicotinib’s FDA Approval
The FDA approval is based on the pivotal Phase 3 MANEUVER trial (NCT05804045), an international, randomized, double-blind, placebo-controlled study evaluating pimicotinib in adults with symptomatic TGCT requiring systemic treatment.
Conducted across 40 specialized centers in Asia, Europe, and North America, the study enrolled 94 patients, randomized 2:1 to receive:
- Pimicotinib 50 mg orally once daily (63 patients).
- Placebo (31 patients).
The initial double-blind treatment period lasted 24 weeks, followed by an open-label phase and a longer-term extension.
The primary endpoint was objective response rate (ORR) at week 25, assessed by blinded independent central review using RECIST v1.1 criteria. Secondary endpoints included tumor volume, joint range of motion, stiffness, pain, physical function, and safety.
According to Merck’s FDA approval announcement, pimicotinib achieved an ORR of 56%, compared with 3% for placebo (p<0.0001).
The original peer-reviewed analysis, published in The Lancet in March 2026, reported response rates of 54% and 3%, respectively, at week 25.
Importantly, the benefits extended beyond tumor shrinkage. Patients receiving pimicotinib experienced statistically significant improvements compared with placebo in:
- Joint range of motion (p=0.0003).
- Physical functioning (p=0.0074).
- Pain (p<0.0001).
These findings are particularly relevant in TGCT, where reducing the size of the tumor is only one aspect of treatment success. Preserving mobility and improving patients’ ability to perform daily activities are equally important clinical goals.
The results were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in The Lancet.
Two-Year MANEUVER Results Show Durable Responses
Longer-term evidence presented at the ESMO Congress 2026 provided additional insight into the durability of pimicotinib’s activity.
At a median follow-up of 22.9 months, the objective response rate among patients initially randomized to pimicotinib reached 76.2% by RECIST v1.1, while response assessed using tumor volume score reached 77.8%.
The median duration of response had not been reached.
Improvements in symptoms and physical functioning were observed as early as week five and were sustained through two years of treatment.
At week 97, patients demonstrated mean improvements from baseline in several important outcomes, including:
- A 19.6% improvement in relative range of motion.
- A 3.9-point reduction in worst stiffness.
- A 3.1-point reduction in worst pain.
- A 7.4-point improvement in PROMIS physical function scores.
At the two-year analysis, 54% of patients initially assigned to pimicotinib remained on treatment.
These longer-term findings suggest that the therapeutic benefits may continue to deepen or remain sustained with ongoing treatment. However, the two-year analysis was conducted during open-label follow-up and did not provide a continued randomized comparison against placebo.
Pimicotinib Safety and Tolerability
The MANEUVER trial also evaluated the safety of pimicotinib, an important consideration for patients who may require prolonged treatment.
During the randomized treatment phase, treatment-emergent adverse events led to dose reductions in 7.9% of pimicotinib-treated patients and treatment discontinuation in 1.6%.
Common adverse events included pruritus, facial and periorbital edema, rash, fatigue, and laboratory abnormalities such as elevated creatine phosphokinase (CPK).
In the peer-reviewed primary analysis, increased CPK was the only grade 3 or 4 treatment-emergent adverse event occurring in more than 10% of pimicotinib-treated patients.
Longer-term follow-up showed no new safety signals, with no evidence of cholestatic hepatotoxicity or drug-induced liver injury reported in the analyzed trial population.
Vinod Ravi, MD, MS, MBA, of The University of Texas MD Anderson Cancer Center and an investigator in the MANEUVER trial, highlighted the drug’s durable tumor response with a manageable tolerability profile. He added:
“This combination of efficacy and safety data will potentially address the needs of people living with TGCT in a once-daily treatment option.”
How Does Pimicotinib Work?
Pimicotinib, originally developed by Abbisko Therapeutics under the designation ABSK021, is a selective inhibitor of colony-stimulating factor-1 receptor (CSF-1R).
The CSF-1/CSF-1R signaling pathway plays a central role in the biology of TGCT by promoting the recruitment and accumulation of macrophages and other cells within the tumor microenvironment. By inhibiting CSF-1R signaling, pimicotinib targets an important mechanism driving tumor growth and local tissue inflammation.
Unlike conventional cytotoxic chemotherapy, pimicotinib is designed to interfere with a specific molecular pathway involved in TGCT development.
An Expanding Treatment Landscape for TGCT
The U.S. approval follows previous regulatory authorizations for pimicotinib in China in December 2025, Canada in June 2026, and Switzerland in October 2026.
The FDA reviewed the application through Project Orbis, an initiative designed to facilitate international collaboration on the review of oncology treatments.
Pimicotinib joins an expanding landscape of targeted systemic treatments for TGCT, including other CSF-1R inhibitors such as pexidartinib and vimseltinib.
The availability of additional therapies may provide clinicians with greater flexibility when selecting treatment based on tumor characteristics, treatment-related risks, and patient priorities. Direct comparative studies would be needed to establish differences in efficacy or safety between these agents.
For patients living with symptomatic TGCT, the approval represents an additional option that addresses not only tumor burden but also the physical limitations associated with this challenging disease.
As longer-term evidence continues to accumulate, understanding treatment durability, tolerability, and the optimal sequencing of available therapies will remain important priorities.
Read further on OncoDaily: FDA approves Vimseltinib(Romvimza) for symptomatic Tenosynovial Giant Cell Tumor (TGCT)
