Background: CSF1R is a clinically validated target for Tenosynovial Giant Cell Tumor (TGCT). CSF1 is overexpressed in TGCT and, via action at the colony-stimulating factor 1 receptor (CSF1R), leads to the proliferation of synovial-like mononuclear cells and recruitment of multinucleate giant cells, foam cells, siderophages, and inflammatory cells, which compose the bulk of the neoplasm. Although nonmetastatic in nature, TGCT can develop into locally destructive lesions that cause significant local tissue injury, loss of joint function, and impaired quality of life. When complete resection is achievable without significant morbidity, the standard of care for patients with TGCT is surgical resection. Recurrence after surgery occurs in up to 30% of patients with localized TGCT and 83% of patients with diffuse TGCT (Mastboom 2019, Patel 2017). Repeat surgeries may be necessary but often leads to further morbidity, complications, and reduced function of affected joints. A safe, effective, and convenient pharmacotherapy is a desirable addition to the therapeutic armamentarium for TGCT. AMB-05X is a potent and selective anti-CSF1R monoclonal antibody in development for local treatment of TGCT. Intra-articular (IA) injection of AMB-05X enables high drug concentration at the tumor site while minimizing systemic exposure and toxicity. A proof-of-concept study of IA AMB-05X for TGCT found clinically meaningful improvement in objective response rate, functional (pain, stiffness, range of motion) and quality of life measures after 12 weeks of therapy with no serious and a low number of adverse events associated with targeting CSF1R. This phase 2 study aims to establish the optimal dosing regimen and local administration of AMB-05X and confirm the efficacy and safety of 24 weeks and longer treatment. Methods: AMB-051-07 (NCT05349643) is an open-label, multicenter, phase 2 study of AMB-05X in patients with TGCT. The trial is being conducted at multiple sites in North America, Europe, and Australia. The dosing schedule includes an injection interval of every 4 weeks and longer, including an extended dosing period. Adult patients with histologically confirmed symptomatic TGCT with one joint involvement whether surgically amenable or non-amenable with measurable disease and adequate organ function are being enrolled. After the initial cohort of patients with TGCT of the knee, other joints may be enrolled pending evaluation by the DMC. The primary study outcome measures are objective response rate (ORR) per RECIST v1.1 by central radiology review and safety. Secondary outcome measures include ORR per modified RECIST and Tumor Volume Score, duration of response, time to response, PRO/QOL (including range of motion, stiffness, pain), pharmacodynamics and pharmacokinetics. Clinical trial information: NCT05349643.