China’s CDE Accepts Marketing Application for Pimicotinib in TGCT

In the phase 3 MANEUVER trial, pimicotinib improved the objective response rate vs placebo in patients with tenosynovial giant cell tumor.

The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted an application seeking marketing authorization for pimicotinib as a Class 1 innovative drug in adult patients with tenosynovial giant cell tumors (TGCTs) who require systemic treatment, according to a press release from the developer, Merck.¹

In May 2024, the CDE granted pimicotinib priority review in the same indication, and the agent has also been granted breakthrough therapy designation by the NMPA. In January 2023, the FDA granted breakthrough therapy designation to pimicotinib in TGCTs.²

Results supporting the indications came from part 1 of the double-blind phase 3 MANEUVER trial (NCT05804045) that evaluated the safety and efficacy of pimicotinib vs placebo in patients with TGCTs. Updated data were most recently shared at the 2025 American Society of Clinical Oncology Annual Meeting.³

“With the acceptance of our application for pimicotinib and the initiation of the priority review, we aim to offer patients in China the first approved systemic therapy for TGCT, addressing a tremendous unmet need in this country,” stated Hong Chow, head of China and international health care business of Merck, in the press release.¹ “Pimicotinib has demonstrated the ability to not only shrink tumors that affect their joints but also improve outcomes like mobility, pain, and stiffness, highlighting its potential to be a best-in-class treatment for TGCT.”

At a data cutoff of September 23, 2024, the objective response rate (ORR) per RECIST v1.1 criteria was 54.0% (95% CI, 40.9%-66.6%) with pimicotinib vs 3.2% (95% CI, 0.1%-16.7%) with placebo, showing a difference of 50.7% (95% CI, 37.0%-64.5%; P < .0001) at week 25. Complete responses (CRs) were achieved by 1 patient in the pimicotinib group and 0 patients in the placebo group; partial responses (PRs) were observed in 33 patients and 1 patient, respectively; stable disease occurred in 20 patients and 28 patients; progressive disease occurred in 2 patients and 0 patients; and 7 and 2 patients were not evaluable.

Additionally, 41.3% of patients treated with pimicotinib achieved an objective tumor response at week 13. It was also noted that pimicotinib’s effect on ORR was consistent among all prespecified subgroups. A decrease in tumor size was observed in 92.1% of the pimicotinib group per blinded independent committee review (BICR).

The ORR using tumor volume score (TVS) was 61.9% (95% CI, 48.8%-73.9%) with pimicotinib vs 3.2% (95% CI, 0.1%-16.7%) with placebo (P < .0001) at week 25. CRs were observed in 1 and 0 patients, respectively; PRs occurred in 38 and 1 patients; stable disease was reported in 16 and 28 patients; progressive disease occurred in 1 and 0 patients; and 7 and 2 patients were not evaluable.

A total of 94 patients were randomly assigned in a 2:1 ratio to receive 50 mg of oral pimicotinib daily for 24 weeks (n = 63) or matching placebo (n = 31) in part 1, of whom all received treatment. In part 2, all patients will be administered pimicotinib at the same dosage and schedule, and then in part 3, all patients who complete the full 24 weeks of dosing in part 2 will be eligible for an extended treatment phase.

Eligible patients were 18 years or older with histologically confirmed unresectable TGCT. Additional enrollment criteria included measurable disease per RECIST v1.1 guidelines with at least 1 lesion of 2 cm or greater and symptomatic disease due to active TGCT.

The trial’s primary end point was ORR by BICR per RECIST v1.1 criteria. Key secondary end points included ORR by BICR per TVS and mean change in clinical outcome assessments such as range of motion, worst pain numeric rating scale (NRS), worst stiffness NRS, and Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) T-score.

Pimicotinib elicited statistically significant and clinically meaningful improvements for clinical outcomes with differences of 15.72 (95% CI, 7.33-24.10; P = .0003) for relative range of motion, –2.44 (95% CI, –3.22 to –1.65; P < .0001) for worst stiffness NRS, –2.09 (95% CI, –2.79 to –1.39; P < .0001) for Brief Pain Inventory worst pain NRS, and 3.40 (95% CI, 0.94-5.86; P = .0074) for PROMIS PF T-scores.

Any treatment-emergent adverse event (TEAE) occurred in 100% of the pimicotinib group vs 93.5% of the placebo group; grade 3 or higher TEAEs occurred in 34.9% and 3.2%, respectively. TEAEs led to dose reduction in 7.9% and 0% of patients, dose interruption in 54.0% and 6.5%, and treatment discontinuation in 1.6% and 0%.

“In parallel, we are working to file a new drug application to the [FDA], with additional filings planned in other markets,” Chow concluded.¹

References

1. China’s Center for Drug Evaluation accepts Merck’s application for marketing authorization of pimicotinib for treatment of tenosynovial giant cell tumor. News release. Merck. June 10, 2025. Accessed June 10, 2025. https://tinyurl.com/37k7df8b
2. Abbisko Therapeutics announces that US FDA has granted breakthrough therapy designation for its CSF-1R inhibitor pimicotinib (ABSK021). News release. Abbisko Therapeutics. January 30, 2023. Accessed June 10, 2025. http://bit.ly/3jk4TXr
3. Niu X, Ravi V, Martin-Broto J, et al. Pimicotinib in tenosynovial giant cell tumor (TGCT): efficacy, safety and patient-reported outcomes of phase 3 MANEUVER study. J Clin Oncol. 2025;43(suppl 16):11500. doi:10.1200/JCO.2025.43.16_suppl.11500