FDA Accepts NDA For Pimicotinib in Tenosynovial Giant Cell Tumors

The FDA has accepted a new drug application (NDA) for pimicotinib as a systemic therapy for patients with tenosynovial giant cell tumors (TGCT), according to a news release from the developer, EMD Serono.¹

Forming the basis of the regulatory action were findings from the phase 3 MANEUVER trial (NCT05804045), in which patients treated with investigational agent experienced a significant improvement in objective response rate (ORR) assessed by blinded independent review committee (BIRC) vs placebo at week 25. Specifically, after a median follow-up of 14.3 months, the investigational agent displayed an ORR of 54% at week 25, increasing to 76.2% by the time of follow-up, according to long-term data presented at the 2025 European Society for Medical Oncology Congress (ESMO)and published in the Annals of Oncology.^2,3By comparison, patients with placebo attained an ORR of 3.2% at 25 weeks (P < .0001).

Additional findings revealed the ORR per BIRC based on tumor volume score (TVS) increased from 61.9% at week 25 in the pimicotinib arm to 74.6% (95% CI, 62.1%-84.7%) by the latest follow-up. Furthermore, the median duration of response (DOR) was not reached (range, 0.03-19.81) in this group, with 93.7% of these patients experiencing a reduction in tumor size per RECIST v1.1 criteria as assessed by BIRC.

Among patients who initially received placebo and switched to pimicotinib, the ORR was 64.5% per RECIST v1.1 and TVS by BIRC after a median follow-up of 8.5 months.

“With pimicotinib, we have an opportunity to significantly advance care for people living with TGCT, a painful and debilitating disease that has few effective and well-tolerated treatment options beyond surgery,” said David Weinreich, global head of Research & Development and chief medical officer for Merck KGaA in Darmstadt, Germany, in the news release on the FDA action.¹ “Based on clinical trial results showing not only a reduction in tumor burden, but also the ability to help alleviate symptoms like pain and stiffness in the global phase 3 MANEUVER study, we are confident in the important role pimicotinib can play for TGCT patients in the US and worldwide.”

Patients with TGCT requiring systemic therapy who did not receive prior anti–CSF-1/CSF-1R therapy in the phase 3 MANEUVER trial were randomly assigned 2:1 to receive 50 mg of daily pimicotinib (n = 63) or placebo (n = 31) for a minimum of 24 weeks. The study was conducted across centers in the US, Canada, Europe, and China. The first part of the trial was double-blind, with eligible patients permitted to continue to the open-label part 2 portion of the trial for an additional 24 weeks of treatment, with a part 3 extension phase permitted for extended treatment and safety follow-up.

The primary end point of the trial was ORR by BIRC per RECIST v1.1 criteria. Secondary end points included TVS, relative range of motion, stiffness by Numeric Rating Scale, and physical function assessed by Patient-Reported Outcomes Measurement Information System (PROMIS-PF).

Among patients who were treated with pimicotinib, no new safety signals emerged after longer-term follow-up. Additionally, there was no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hypopigmentation of the skin or hair. Most treatment-emergent adverse effects were mild and manageable.

Pimicotinib was approved by the China National Medical Products Administration (NMPA) as a treatment for adult patients with symptomatic TGCT who were not recommended for surgical resection in December 2025.

References

1. FDA accepts new drug application for pimicotinib for the treatment of tenosynovial giant cell tumor. News release. EMD Serono. January 12, 2026. Accessed January 13, 2026. https://tinyurl.com/3wzyyyeh
2. Gelderblom H, Ravi V, Martin-Broto J, et al. 2690MO: 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):1340-1341. doi:10.1016/j.annonc.2025.08.3301
3. Pimicotinib treatment demonstrates deep and durable tumor responses and continued improvements in pain and function for patients with TGCT. News release. EMD Serono. October 17, 2025. Accessed January 13, 2026. https://tinyurl.com/bdz7v7p5