FDA Approves Pimicotinib for Tenosynovial Giant Cell Tumors

The FDA has approved pimicotinib (Pimjetmi) for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for whom surgical resection may cause worsening functional limitation or severe morbidity, according to a news release from the FDA.¹

The recommended dosage of pimicotinib is 50 mg orally once daily with or without food. The prescribing information for pimicotinib includes warnings and precautions for hepatotoxicity, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

The regulatory decision is supported by findings from the global phase 3 MANEUVER trial (NCT05804045), in which once-daily pimicotinib produced deep and durable tumor responses alongside meaningful improvements in symptoms and physical function.² The FDA accepted the new drug application (NDA) for pimicotinib in January 2026.

At the time of the NDA acceptance, David Weinreich, global head of R&D and chief medical officer for the Healthcare business of Merck KGaA, Darmstadt, Germany, said pimicotinib offered an opportunity to “significantly advance care for people living with TGCT,” citing both reductions in tumor burden and relief of symptoms such as pain and stiffness in the trial.²

MANEUVER is a 3-part, randomized, double-blind, placebo-controlled study evaluating pimicotinib in patients with TGCT who require systemic therapy and had not previously received anti-CSF-1/CSF-1R therapy. In part 1, 94 patients were randomly assigned 2:1 to receive pimicotinib at 50 mg once daily (n = 63) or placebo (n = 31) for 24 weeks. After part 1, eligible patients could continue to open-label treatment in part 2 for up to 24 weeks and then enter an open-label extension (part 3). Patients were enrolled in China (n = 45), Europe (n = 28), and the US and Canada (n = 21).²

The primary end point was objective response rate (ORR) at week 25 per RECIST v1.1 by blinded independent review. Secondary end points included tumor volume score (TVS), relative range of motion (ROM), stiffness by Numeric Rating Scale, pain by Brief Pain Inventory, and physical function by Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF).²

The trial met its primary end point, with pimicotinib producing an ORR of 54.0% compared with 3.2% for placebo at week 25 (P <.0001).³ The study also demonstrated statistically significant and clinically meaningful improvements in all secondary end points, including active ROM and physical function, as well as reductions in stiffness and pain.²

Responses deepened with longer follow-up. At a median follow-up of 14.3 months, patients treated with pimicotinib from baseline achieved an ORR of 76.2% (95% CI, 63.8%-86.0%) per RECIST v1.1 and 74.6% (95% CI, 62.1%-84.7%) by TVS, with 6- and 12-month duration of response (DOR) rates of 98% and 92%, respectively. Patients who crossed over from placebo achieved an ORR of 64.5%.³

Two-year data presented at the ESMO Congress 2026 showed that at a median follow-up of 22.9 months, the ORR by RECIST v1.1 was maintained at 76.2%, the ORR by TVS increased to 77.8% (95% CI, 65.5%-87.3%), and the complete response rate by RECIST v1.1 rose to 7.9% from 1.6% at week 25. Median DOR was not reached, and 54.0% of patients remained on treatment. At week 97, patients had a mean 19.6% improvement in ROM, a 7.4-point increase in PROMIS-PF T-score, and reductions of 3.9 and 3.1 points in worst stiffness and worst pain, respectively.⁴

Regarding safety at 2 years, 27.0% of patients had a treatment-emergent adverse event (TEAE) leading to dose reduction and 7.9% had a TEAE leading to discontinuation, with a median dose intensity of 84.8%. The most common TEAEs included increased blood creatine phosphokinase (71.4%), pruritus (60.3%), lactate dehydrogenase increase (58.7%), aspartate aminotransferase increase (55.6%), face edema (49.2%), rash (38.1%), and periorbital edema (36.5%). Investigators reported no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair hypopigmentation.⁴

References

1. FDA approves pimicotinib for symptomatic tenosynovial giant cell tumor. News release. FDA. November 10, 2026. Accessed November 10, 2026. https://tinyurl.com/7dtvbwfc
2. 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
3. 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.
4. 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.