A new drug application (NDA) has been accepted by the FDA seeking the approval of pimicotinib (ABSK021) for the systemic treatment of patients with tenosynovial giant cell tumor (TGCT).1
The NDA is supported by efficacy and safety findings from the global, multicenter, randomized, double-blind, placebo-controlled phase 3 MANEUVER trial (NCT05804045), which evaluated once-daily oral pimicotinib, a highly selective and potent small-molecule colony-stimulating factor 1 receptor (CSF-1R) inhibitor, in patients with TGCT.
Longer-term results presented at the 2025 ESMO Congress showed that at a median follow-up of 14.3 months, patients treated with pimicotinib from baseline (n = 63) achieved an overall response rate (ORR) of 76.2% (95% CI, 63.8%-86.0%) by blinded independent review committee (BIRC) per RECIST 1.1 criteria.2 The BIRC-assessed ORR by tumor volume score (TVS) was 74.6% (95% CI, 62.1%-84.7%). Best responses per RECIST 1.1 criteria included complete response (6.3%), partial response (69.8%), stable disease (19.0%), and progressive disease (0%); 4.8% of patients were not evaluable for response. The 12-month duration of response (DOR) rate was 92% (95% CI, 70%-98%).
Pimicotinib in TGCT At a Glance
- The FDA accepted the NDA seeking the approval of pimicotinib as a systemic therapy for TGCT, supported by findings from the MANEUVER trial.
- Data presented at the 2025 ESMO Congress showed that at a median follow-up of 14.3 months, pimicotinib produced a BIRC-assessed ORR of 76.2% (95% CI, 63.8%-86.0%) per RECIST 1.1 criteria; best responses included a 6.3% complete response rate and a 69.8% partial response rate.
- MANEUVER included a 24-week randomized, double-blind, placebo-controlled period followed by a portion where patients received open-label pimicotinib for 24 weeks, with an open-label extension for longer-term treatment and follow-up.
How was the MANEUVER trial designed?
The MANEUVER trial incorporated a design with a structured transition to open-label treatment across 3 study parts.3 In part 1, patients were randomly assigned to receive either oral pimicotinib capsules or matching placebo for 24 weeks under blinded conditions.
Part 2 of the study was an open-label phase in which all patients received open-label pimicotinib for an additional 24 weeks or until withdrawal. Patients who completed part 2 and continued to meet eligibility criteria were permitted to proceed to part 3, an open-label extension portion, during which pimicotinib was administered until study completion, patient withdrawal, or sponsor-directed termination.
ORR served as the primary end point. Secondary end points included ORR per TVS; mean change from baseline at week 25 in range of motion, worst pain, and worst stiffness; patient-reported outcomes, quality of life, and DOR.
How were patients selected for enrollment in the MANEUVER trial?
Eligible patients were required to be at least 18 years of age with histologically confirmed TGCT. Enrollment focused on patients for whom surgery was not optimal, including those in whom resection could result in functional impairment or serious complications, as well as those with tumors in complex anatomic locations or with extensively invasive disease that was not amenable to complete resection.4
Patients also needed to have symptomatic disease because of active TGCT, defined as at least moderate pain or stiffness, and measurable disease by RECIST 1.1 criteria, including more than 1 lesion measuring at least 2 cm, as assessed by MRI. Adequate organ and bone marrow function per screening laboratory assessments was required.
Key exclusions included prior exposure to highly selective CSF-1 or CSF-1R inhibitors (with prior imatinib and/or nilotinib permitted), metastatic TGCT, or receipt of major surgery or antitumor therapy for TGCT within 4 weeks prior to random assignment.
What adverse effects characterize the safety profile of pimicotinib?
In the most recent analysis of the MANEUVER trial, the most frequently reported treatment-emergent adverse effects (AEs) associated with pimicotinib included pruritus (all-grade, 60.3%; grade 3/4, 3.2%), facial edema (49.2%; 0%), rash (38.1%; 6.3%), periorbital edema (36.5%; 0%), fatigue (28.6%; 0%), nausea (28.6%; 0%), and headache (25.4%; 0%).2 The rates of laboratory abnormalities were led by creatine phosphokinase elevation (all-grade, 71.4%; grade 3/4, 15.9%), followed by any-grade increases in levels of lactate dehydrogenase (57.1%), aspartate aminotransferase (55.6%), amylase (38.1%), lipase (27.0%; grade 3/4, 3.2%), alpha-HBDH (25.4%), blood creatine kinase MB (20.6%), and alanine aminotransferase (22.2%), with no grade 3/4 AEs reported for most parameters.
References
- Abbisko Therapeutics announces FDA acceptance of the NDA for pimicotinib for the treatment of tenosynovial giant cell tumor. News release. Abbisko Therapeutics Co. Ltd. January 13, 2026. Accessed January 13, 2026. https://www.abbisko.com/newsDetail/234.html
- 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
- Study of pimicotinib (ABSK021) for tenosynovial giant cell tumor (MANEUVER). ClinicalTrials.gov. Updated September 8, 2025. Accessed January 13, 2026. https://www.clinicaltrials.gov/study/NCT05804045#study-plan
- Niu X, Ravi V, Shan B, et al. MANEUVER: a phase III study of pimicotinib to assess efficacy and safety in tenosynovial giant cell tumor patients. Future Oncol. Published online September 17, 2024. doi:10.1080/14796694.2024.2396227
