Pimicotinib Responses Deepen Over 2 Years in Tenosynovial Giant Cell Tumor

Treatment with pimicotinib (ABSK021) produced tumor responses that deepened and remained durable through 2 years in patients with tenosynovial giant cell tumor (TGCT), along with continued improvements in stiffness, pain, and physical function, according to a 2-year analysis of the phase 3 MANEUVER trial (NCT05804045) presented at the ESMO Congress 2026.¹

At a median follow-up of 22.9 months (range, 2.6-33.6), the objective response rate (ORR) per blinded independent review committee (BIRC) assessment by RECIST v1.1 was 76.2% (95% CI, 63.8%-86.0%) among patients initially randomly assigned to pimicotinib, which was unchanged from the 1-year analysis. The ORR by tumor volume score (TVS) increased from 74.6% (95% CI, 62.1%-84.7%) at 1 year to 77.8% (95% CI, 65.5%-87.3%) at 2 years. Median duration of response (DOR) was not reached.

Investigators, led by first author Hans Gelderblom, MD, PhD, medical oncologist and chair of the department of Medical Oncology at the Leiden University Medical Center, concluded that the findings support pimicotinib as a treatment that offers sustained long-term benefit, durable antitumor activity, and a predictable safety profile in patients with TGCT.

MANEUVER is a global, randomized, double-blind, placebo-controlled phase 3 trial conducted at 40 sites, including 23 in China, 10 in North America, and 7 in Europe. Adults with symptomatic, histologically confirmed, unresectable, and measurable TGCT were randomly assigned 2:1 to receive pimicotinib at 50 mg once daily or placebo for 24 weeks in part 1. Eligible patients could then continue to a 24-week open-label phase (part 2) followed by an open-label extension (part 3). The primary end point was ORR per BIRC by RECIST v1.1 at week 25; secondary end points included ORR by TVS, clinical outcome assessments of range of motion (ROM), stiffness, pain, and physical function, and safety. The 2-year data cutoff was March 1, 2026, corresponding to week 97.

The trial previously met its primary end point, with pimicotinib producing an ORR of 54.0% vs 3.2% with placebo at week 25 (P <.0001). Longer-term data presented at ESMO 2025 showed that the ORR rose to 76.2% at a median follow-up of 14.3 months.²

In the current analysis, 63 patients were initially randomly assigned to pimicotinib. The median age was 41.0 years (range, 31-52), 71.4% of patients were female, diffuse TGCT was the most common subtype (84.1%), and the knee was the most common tumor location (52.4%). At the 2-year cutoff, 34 patients (54.0%) remained on treatment, and the median treatment duration was 22.5 months (range, 1.8-33.6).

Responses deepened with continued treatment. The complete response (CR) rate by RECIST v1.1 increased from 1.6% at week 25 to 6.3% at 1 year and 7.9% at 2 years; the CR rate by TVS rose from 1.6% at week 25 to 9.5% at 2 years. Best responses per RECIST v1.1 at 2 years included partial response (68.3%), stable disease (19.0%), progressive disease (0%), and not evaluable (4.8%). Responses were ongoing across a DOR range of 0.03+ to 26.18+ months, and the 2-year DOR rate was 82% (95% CI, 64.0%-92.0%).

Improvements in TGCT-related symptoms and function were observed at the first assessment and continued through 2 years. At week 97, mean changes from baseline included a 19.6% improvement in relative ROM (standard error [SE], 4.7), a 7.4-point increase in Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) T-score (SE, 1.1), a 3.9-point reduction in worst stiffness (SE, 0.3), and a 3.1-point reduction in worst pain (SE, 0.4).

The safety profile remained consistent between 1 and 2 years, with no new safety signals. Overall, 17 patients (27.0%) had a treatment-emergent adverse event (TEAE) leading to dose reduction, and 5 (7.9%) had a TEAE leading to discontinuation; between years 1 and 2, only 1 additional patient had a dose reduction and 1 additional patient discontinued treatment. The median dose intensity was 84.8% (range, 41.3%-100.5%). Investigators reported no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair hypopigmentation.

The most common laboratory TEAEs of any grade at 2 years were increased blood creatine phosphokinase (CPK; 71.4%), lactate dehydrogenase (58.7%), aspartate aminotransferase (55.6%), amylase (38.1%), and lipase (28.6%). The most common clinical TEAEs included pruritus (60.3%), face edema (49.2%), rash (38.1%), periorbital edema (36.5%), fatigue (30.2%), nausea (28.6%), headache (25.4%), and insomnia (20.6%). At the 1-year cutoff, grade 3 or higher events included CPK increase (15.9%), rash (6.3%), pruritus (3.2%), and lipase increase (3.2%).

In January 2026, the FDA accepted a new drug application for pimicotinib as a systemic treatment for patients with TGCT based on primary and longer-term MANEUVER results.³ Pimicotinib was approved in China in December 2025 and holds FDA breakthrough therapy designation for inoperable TGCT.⁴

References

1. Gelderblom H, Ravi V, Martin Broto J, et al. Pimicotinib in patients with tenosynovial giant cell tumour: 2-year analysis of the phase 3 MANEUVER trial. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Poster 3747P.
2. Niu X, Ravi V, Broto JM, et al. Extended efficacy and safety from the phase 3 MANEUVER trial of pimicotinib in patients with tenosynovial giant cell tumour. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2690.
3. FDA accepts new drug application for pimicotinib for the treatment of tenosynovial giant cell tumor. News release. EMD Serono. January 12, 2026. Accessed October 26, 2026. https://tinyurl.com/3wzyyyeh
4. Pimicotinib approved as systemic treatment in China for tenosynovial giant cell tumor. News release. Merck KGaA. December 22, 2025. Accessed December 22, 2025. https://tinyurl.com/5adfvsvu