Squamous cell carcinoma is the most frequently occurring malignant tumor in the head and neck. More than 90% of head and neck squamous cell carcinomas (HNSCC) originate from the mucosal linings of the oral cavity, pharynx, or larynx. The estimated worldwide incidence of HNSCC in 2012 was approximately 686,000, with approximately 375,000 deaths.1 Oral cavity cancer in particular is a significant and growing problem in many parts of the world, with an estimated annual incidence of around 275,000.2

Despite improvements in therapy, recurrent disease remains frequent and is generally treated with radiation therapy, chemotherapy, biological therapy, or a combination of these modalities.3,4 Recurrence and death, however, are closely correlated, with median survival rates of only 3 to 9 months. In oral cavity cancer, five-year survival rates are around 50%, but successfully treated patients may still have to cope with consequences of their treatment that affect appearance, function, and quality of life. Clearly, better therapies in the first-line setting are needed.

The focus of the INSPIRE study is cancer of the oral cavity, which was selected in part because of the limitations of currently available therapies. In addition, there is evidence that the impact of the immune system upon HNSCC differs by tumor site.5 Thus, in order to maximize the ability to detect benefit conferred by immune modulation by the IRX-2 regimen, a homogenous patient population with respect to site and standard treatment modality is required. In addition, relatively few new therapeutic approaches directed to cancer of the oral cavity are being investigated.


Subjects with HNSCC are consistently found to have disordered immune function at the time of presentation. Although they have normal B-cell function, immunoglobulin levels, and complement systems, HNSCC patients have immunological deficiencies of T-cell anergy and defective monocyte/macrophage function.6,7

The cumulative result of the various immune defects and immunosuppressive mechanisms in HNSCC is8:

  • The tumor successfully subverts the antigen presentation component (ie, dendritic cells) and the responding T-cell component of immunization, even though the tumor displays and sheds antigens capable of inducing immunization and tumor rejection
  • The compromised cellular immune response is, therefore, incapable of inducing tumor rejection

© 2016 IRX Therapeutics