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AMB-05X for TGCT


Licensed from Amgen, AMB-05X is a human monoclonal antibody against the CSF1R and is the only pharmacological treatment administered locally and directly at the tumor site for tenosynovial giant cell tumor (TGCT).  Positive results from a Phase 2 proof-of-concept study demonstrated clear benefits across multiple clinically relevant endpoints, including tumor reduction measured by MRI, with an improved safety profile.   AMB-05X has received Fast Track and PRIME designations from the FDA and European Medicines Agency, respectively. 

This novel therapeutic approach via intra-articular administration achieved the objective response rate targets after only 12 weeks of treatment and showed trends for continuing tumor shrinkage beyond the dosing period, with minimal systemic exposure and significantly fewer adverse events than reported in other TGCT trials.  Patient-reported clinical efficacy parameters such as worst pain and stiffness in the affected joint were also markedly improved.  These data suggest that treatment with AMB-05X could offer physicians and patients a more convenient and potentially much safer treatment option, enabling its potential application in a much larger TGCT patient segment unserved by the systemically administered agents.


AmMax is enrolling patients in its Phase 2b program with a treatment duration of six months, in line with the common duration of systemic pharmacological interventions, to demonstrate even greater tumor reduction with once-monthly treatments and evaluate dose optimization for its Phase 3 study design.

Disease and Prevalence

Previously known as pigmented villonodular synovitis (PVNS), TGCT is a non-malignant but locally aggressive tumor of the synovium in musculoskeletal joints that results in significant joint damage, painful swelling, and debilitating functional impairments.  

TGCT lesions typically present between the ages of 30 and 50 years as either localized (L-TGCT) or diffuse (D-TGCT) disease (1). L-TGCT involves mainly the digits and wrist and less frequently larger joints. D-TGCT involves mainly large joints – particularly the knee (60-75% of the cases), but also hip, ankle, shoulder and elbow, and it is locally invasive. TGCT are typically intra-articulate but D-TGCT can become extra-articular (2). Typically, only one joint is affected. 

Diffused TGCT tumor of the knee.png

Figure 1. Diffuse TGCT tumor of the knee. Sagittal T1 MRI of the knee illustrates (✰) tenosynovial giant cell tumor extending throughout the joint. Also shown is erosion into the tibial plateau (  ) and secondary osteoarthritis (     )

A 23 year old femail with L-TGCT.png

Figure 2. A 23-year-old female with L-TGCT

L-TGCT is much more common compared to D-TGCT with a ratio of approximately 10:1. The combined incidence rate is estimated at roughly 4.3 in 100,000, translating into ~40,000 new cases per year in the US and the European Union and more than 300,000 cases per year worldwide (1,3,4).

Pathogenesis and AMB-05X Mechanism of Action

TGCT is caused by excessive production of CSF1. A small proportion of the TGCT cells are neoplastic with translocation at the CSF1 gene locus resulting in the dysregulated CSF1 levels which then acts at the CSF1 Receptor (CSF1R) to expand the neoplastic cells and attract immature myeloid cells and inflammatory cells, including macrophages, which then comprise the bulk of the tumor (5,6).

AMB-051 MoA.png

AMB-05X is a monoclonal antibody against the CSF1R, inhibiting CSF1 action in vivo (7). As inhibition of CSF1 action at the CSF1R has been proven effective against TGCT in clinical studies (8,9), CSF1R represents a clinically validated target for the treatment of TGCT.

Current Treatment & Unmet Need

Treatment is individualized based on disease progression, types of TGCT, location of the tumor mass and expected post-operative morbidity. In general, surgical resection is the first line treatment for L-TGCT. It can be effective although it often requires extended rehabilitation (Sarcoma Advisory Group) adding to the disease burden. D-TGCT is surgically problematic, difficult to remove completely and often requires a total synovectomy, or at times a joint replacement, or even amputation. Recurrence occurs in up to 15% of L-TGCT patients and up to 50% of D-TGCT patients who undergo surgical resection (2, Sarcoma Advisory Group). For these patients, the prognosis is grim with severe long-term morbidity and poor quality of life.

An oral small molecule CSF-1 R kinase inhibitor, pexidartinib, was approved in 2019 for the treatment of symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. The approval of pexidartinib, as the first pharmacological agent, created much optimism among physicians for a potential breakthrough in the management of TGCT and provided validation of CSF1R as a therapeutic target. However, pexidartinib carries a black-box warning for  hepatotoxicity  and  notation that such severe liver problems may lead to death. According to its label the drug could only be prescribed to the small segment of TGCT patients who are deemed non-amenable to surgery as a first option.  In addition, pexidartinib is associated with substantial undesirable side effects such as edema (10). Given the non-life-threatening nature of this debilitating disease, pexidartinib's side effect profile is problematic and limiting in terms of a broader applicability. In fact, the EMA rejected pexidartinib's MAA in June 2020, citing unfavorable side effect profiles.

There remains a significant unmet need for a safe and efficacious pharmacological agent that serves the diverse population of TGCT patients, including as an alternative to those otherwise amenable to surgery, to avoid surgical morbidity or reduce  postoperative  recurrence rate. AMB-05X has a therapeutic profile that would potentially meet the significant unmet need and provide unprecedented pharmacotherapy benefit for patients suffering from TGCT.

AMB-05X Differentiation

AmMax’s patented novel delivery approach enables local administration and capitalizes on desirable AMB-05X physico-chemical and biological properties to optimize efficacy and minimize potential side effects. This Best-in-Class profile would afford an opportunity to serve a broader segment of patients and provide a viable alternative to surgical intervention.


  1. Mastboom MJL et al., Acta. Orthop. 2017; 88:688

  2. Gouin F and Noailles T, Orthopaed. & Traumatol.: Surg. & Res. 2017; 103:S91–S97

  3. Ehrenstein V et al., J. Rheumatol. 2017; 44:1476

  4. ORPHA:66627

  5. West RB et al., Proc. Natl. Acad. Sci. USA 2006; 103:690

  6. Cupp JS et al., Am. J. Surg. Pathol 2007; 31:970

  7. Papadopoulos KP et al., Clin. Cancer Res. 2017; 23:5703

  8. Cassiere PA et al., Lancet Oncology 2015; 16:949

  9. Tap WD et al., Lancet 2019; 394:478

  10. TURALIOTM (pexidartinib) prescribing information (08/2019)

Figure 1:

Figure 2: Krishna D, et al., J. Orthopaed. Traumatol. Rehab. 2017; 9:115

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