Novel Anti-CSF1 Receptor Antibody for Patients With Tenosynovial Giant Cell Tumor
According to a phase 2a trial, the novel anti-CSF1 receptor monoclonal antibody, AMB-05X, was found to have favorable pharmacokinetics, pharmacodynamics, efficacy, and safety among patients with tenosynovial giant cell tumors (TGCT).
Testing of AMB-05X was first done on normal monkeys, with 5 mg/kg administered intra-articularly. Following those results, there was a multi-center, single-arm phase 2a study, including 11 patients with TGCT. Patients received either 150 mg (n = 8) or 90 mg (n = 3) administered to the affected knee, every 2 weeks for 12 weeks total. Evaluated outcomes included safety, efficacy, pharmacokinetics, pharmacodynamics, and anti-drug antibody. Efficacy was determined by tumor response as assed on MRI and patient-reported outcomes.
In the monkey cohort, the intra-articular pharmacokinetic included long synovial residence and low systemic exposure. The most common low-grade treatment-emergent adverse events were edema, fatigue, arthralgia, rash, and pruritus or hypertension, with lower events occurring in the 90 mg cohort compared to the 180 mg cohort. With the twice weekly dosing, there was an accumulation of high synovial vs systemic AMB-05X (pharmacokinetic) and CSF1 (pharmacodynamic) levels. The objective tumor response was 36% overall with RECISTv1.1, and 45% with Modified RECIST. There was a significant improvement of patient-reported outcomes at 10 to 12 weeks. The anti-drug antibody was 0%.
With this study, favorable pharmacokinetic, pharmacodynamic, efficacy, and safety/tolerability of intra-articular administration of this anti-CSF1R monoclonal antibody was validated. Study authors commented these results “support further development of this novel treatment approach.”
Source:
Van de Sande M, Johnson K, van Langevelde K, et al. Pharmacokinetics and pharmacodynamics of an anti-CSF1 receptor antibody in the intra-articular treatment of tenosynovial giant cell tumor. Eur J Cancer. Published online September 5, 2025. doi:10.1016/j.ejca.2025.115756
