FDA Approves Pimicotinib for Symptomatic TGCT

The FDA has approved pimocotinib (Pimjetmi) for patients with symptomatic tenosynovial giant cell tumor (TGCT) in whom surgical resections could potentially worsen functional limitations or severe morbidity.¹

The regulatory decision was based on data from the phase 3 MANEUVER trial (NCT05804045). Earlier data from the trial which were were presented at the 2025 European Society for Medical Oncology Congress showed an overall response rate (ORR) by blinded independent central review (BICR) of 76.2% (95% CI, 63.8%-86.0%) for pimicotinib (n = 63), in addition to a BIRC-assessed ORR per tumor volume score (TVS) of 74.6% (95% CI, 62.1%-84.7%).² Notably, the median duration of response (DOR) was not reached (range, 0.03-19.81 months) for these patients.

Regarding safety, the most common adverse effects (AEs) that occurred in at least 20% of patients were pruritus, rash, face edema, periorbital edema, fatigue, nausea, headache, and peripheral edema.¹

“We are moving toward a model where tumor biology informs not only survival but how well patients function, and that is a meaningful evolution for our field,” said R. Lor Randall, MD, FACS, who serves as the David Linn Endowed Chair for Orthopaedic Surgery, the chair of the Department of Orthopaedic Surgery, and a professor at the University of California Davis Comprehensive Cancer Center in Sacramento, stated in an interview with OncLive® about the trial.

How was the MANEUVER trial designed?

The randomized, open-label trial enrolled patients who were at least 18 years of age that had a confirmed diagnosis of symptomatic TGCT and measurable disease with at least 1 lesion that was at least 2 cm.^1,3 Patients with also needed to have an ECOG performance status of 1 or less and adequate bone marrow and organ function.³

If patients had received prior treatment with a CSF-1 inhibitor, had a known additional malignancy that required active treatment, metastatic TGCT, significant concomitant arthropathy in the affected joint, uncontrolled infections, or major surgery or previous anti-tumor therapy for TGCT within 4 weeks prior to randomization, they were not included in the trial.

Patients were randomly assigned to receive 50 mg of pimicotinib once daily or placebo.^1,3 Patients in the placebo arm received the matching placebo for 24 weeks in part 1 of the trial before having the option to switch to pimicotinib in part 2 of the trial.³ Additionally, randomization was stratified by geographic region, specifically those in China and those not in China.¹

ORR per RECIST 1.1 criteria was the trials primary end point, whereas ORR per TVS and change from baseline in active range of motion, worst stiffness numeric rating scale (NRS) score, brief pain inventory worst pain NRS score, and patient-reported outcomes measurement information system physical function score, all assessed at week 25, were secondary end points.³

Baseline characteristics revealed that patients had a median age of 40 years (range, 18–69) and were mostly female (68.1%). Nearly half of patients were located in China (47.9%).

“Multiple agents are now available, and some patients do very well on current therapies. If it isn’t broken, don’t fix it; the latest and greatest doesn’t mean you should necessarily switch a patient off a prior agent if they are doing well with it, because these drugs are wonderful in certain patients but have AEs in others,” Randall explained. “As patients are started on treatment, some of these newer agents will be chosen because the specificity and mechanistic biology are getting increasingly refined”

What are the next steps and important considerations with pimicotinib?

“These findings build on [data with] prior [systemic] agents such as pexidartinib [Turalio], and more recently, vimseltinib [Romvimza] and suggest a potentially improved therapeutic index with a highly selective CSF-1R inhibitor,” Randall explained. “This [trial] fundamentally changes our treatment paradigm. Instead of viewing these patients as surgical problems with limited options, we can now integrate systemic therapy to downstage disease, improve symptoms, and, in some cases, avoid or even defer surgery. It’s exciting to me as a surgeon as well as an academic oncologist.”

“Those of us who see enough of these patients are really backing away from up-front surgical management for diffuse TGCT. For nodular TGCT, there is still a role for surgery. Having said that, for advanced, bulky disease, most of us with [substantial] experience are backing away from offering surgery up front,” he concluded. “All of this is very nuanced, which brings me back to that fundamental tenet: It needs to be a combined effort from a multidisciplinary team.”

References

1. FDA approves pimicotinib for symptomatic tenosynovial giant cell tumor. FDA. November 10. 2026. Accessed November 10, 2026. https://www.fda.gov/drugs/cancer-approvals/fda-approves-pimicotinib-symptomatic-tenosynovial-giant-cell-tumor?utm_medium=email&utm_source=govdelivery
2. Gelderblom H, Ravi V, Martin-Broto J, et al. Extended efficacy and safety from the phase III MANEUVER trial of pimicotinib in patients with tenosynovial giant cell tumour (TGCT). Ann Oncol. 2025;36(suppl 2):S1340-S1341. doi:10.1016/j.annonc.2025.08.3301
3. Study of pimicotinib (ABSK021) for tenosynovial giant cell tumor (MANEUVER). ClinicalTrials.gov. Updated May 4, 2026. Accessed November 10, 2026. https://clinicaltrials.gov/study/NCT05804045?id=NCT05804045&viewType=Card&rank=1