emactuzumab (RG7155)

P3, N=128, Active, not recruiting, SynOx Therapeutics Limited | Trial primary completion date: Apr 2026 --> Dec 2025

P3, N=1000, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P3, N=128, Recruiting, SynOx Therapeutics Limited | Trial primary completion date: Sep 2027 --> Apr 2026

P3, N=128, Not yet recruiting, SynOx Therapeutics Limited | Trial completion date: Sep 2025 --> Sep 2027 | Trial primary completion date: Dec 2023 --> Sep 2027

P2, N=9, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; The study was terminated early by the Sponsor

Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

Systemic agents such as tyrosine kinase inhibitors (e.g., nilotinib and imatinib) or agents targeting the CSF-1 (colony-stimulating factor-1) pathway (e.g., pexidartinib and emactuzumab) are active against TGCT. This will also reduce the risk of a postoperative nerve palsy.Although separate instruments for the anterior and posterior portions of the procedure are not necessary, separate drapes, gown, and gloves and other preoperative preparation should be readied in advance for the second portion of the procedure in order to save operative time. PVNS = pigmented villonodular synovitisROM = range of motionMRI = magnetic resonance imagingGastroc = gastrocnemiusPDS = polydioxanone sutureCAM = controlled ankle motionASA = acetylsalicylic acid (aspirin).

While the majority of diffuse TSGCT harbor CSF1 fusion, targetable by imatinib, emactuzumab, and nilotinib, cases with malignant transformation (MTSGCT) have not responded to CSF1-R inhibitors. MTSGCT is at least an intermediate grade sarcoma of histiocytic phenotype of the knee, the majority with untoward outcome. Histologic criteria have been established for malignant transformation of diffuse TSGCT. Further studies are ongoing to identify possible alternate targets to CSF1-R in rare MTSGCT.

Emactuzumab in combination with atezolizumab demonstrated a manageable safety profile with increased fatigue and skin rash over usual atezolizumab monotherapy. A considerable ORR was particularly seen in ICB-experienced NSCLC patients. Increase ofCD8 +TILs under therapy appeared to be associated with persistence of a TAM subpopulation.

TGCT is a rare, localized neoplasia of the joints. Although non-lethal, it may cause important functional impairments, significant joint damage, and decline in quality of life for otherwise young and healthy individuals.The level and duration of the emactuzumab dose regimen has been selected based on the Phase I results to maximize the depletion of CSF-1R macrophages, whilst minimizing the potential for toxicity. Subjects will be closely monitored throughout the study for safety, efficacy, and QoL.

Patients who developed edema in response to emactuzumab had elevated HA in peripheral blood. Our findings indicate that an early increase of peripheral HA can serve as a pharmacodynamic marker for edema development and suggest potential interventions based on MMP inhibition for relieving periorbital edema in patients treated with CSF1R inhibitors.