Phase II Trial of HM781-36B in Patients With Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of or Unfit for Platinum-containing Therapy

Head and neck cancer is the sixth most common cancer and more than 650,000 new cases are diagnosed each year worldwide. About 60% of the HNSCC patients present with unresectable locally advanced disease at diagnosis and treated with multimodality approach. Despite such approach, majority (70%) of patients develop local or/and regional recurrences. Additional 10% of patients present with distant metastasis at diagnosis. Most patients with recurrent or metastatic disease are treated with single agent chemotherapy, combination chemotherapy or targeted therapies. Despite its public health magnitude, HNSCC in Asian countries has received a limited attention for the drug development and cancer-related research. In fact, HNSCC ranked 7th among men and 10th among women by incidence in China, the largest producer and consumer of tobacco and alcohol. Recently, Chen et al. documented a 1:1:2 subset distribution for cancers of oral cavity, pharynx, and larynx in China, similar to the distribution reported in Korea but quite different from the general distribution of 5:2:3 in whites. Ethnic disparities in HNSCC also include its prognosis and this is partly explained by HPV-active disease ratio and genetic factors. Therefore, there is a strong need for an additional research in patients with HNSCC in Asia. Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with HNSCC. The association between EGFR-activated signaling pathways and tumor cell survival are well documented in many studies. EGFR targeting strategies showed clinical anti-tumor efficacy in patients with HNSCC, especially with monoclonal antibody, cetuximab. In the Extreme study, it was shown that the addition of cetuximab to platinum-5-FU significantly prolonged the median overall survival from 7.4 months to 10.1 months compared to platinum-5FU alone in the first-line setting. HM781-36B is a irreversible pan-HER inhibitor. In preclinical studies, HM781-