A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck

Abstract

VB4-845 is a novel recombinant fusion protein that targets the epithelial cellular adhesion molecule (EpCAM). This initial clinical trial was conducted to determine the maximum tolerated dose of intratumoral injections in patients with advanced squamous cell carcinoma of the head and neck and to assess pharmacokinetics and immunogenicity. Twenty-four patients with advanced, recurrent squamous cell carcinoma of the head and neck received two cycles of five daily intratumoral VB4-845 injections of 20, 40, 80, 130, 200, or 280 microg. The maximum tolerated dose was established to be 280 microg administered daily for 5 days. Common adverse events were pain due to intratumoral injection and reversibly elevated liver enzymes. Of the 24 patients, 15 had detectable blood levels with a mean drug half-life of 4.0 +/- 0.3 h. VB4-845 reduced or stabilized tumors in 71.4% of epithelial cell adhesion molecule-positive patients. VB4-845 intratumoral injection therapy was well tolerated and feasible.

Expression of epithelial cell adhesion molecule (EpCAM) in oral squamous cell carcinoma

“…Recently, many studies have focused upon EpCAM as a favourable target for tumour therapy, involving monoclonal and bi-/tri-specific antibodies and vaccination strategies. 7,46,47 Thus, the data from our study add to the growing body of evidence that EpCAM plays a role in the carcinogenesis of oral cancer. We suggest that this marker could be used to identify more aggressive types of OSCC having poorer differentiation with more chance of recurrence, and also serves as a potential biomarker in predicting the survival in OSCC cases.…”

“…Based on the fact that EpCAM plays a role in carcinogenesis, it is simplistic to believe that it could serve as a potential therapeutic target in cancer. Recently, many studies have focused upon EpCAM as a favourable target for tumour therapy, involving monoclonal and bi‐/tri‐specific antibodies and vaccination strategies . Thus, the data from our study add to the growing body of evidence that EpCAM plays a role in the carcinogenesis of oral cancer.…”

Expression of Ep‐CAM, but not of E48, associates with nodal involvement in advanced squamous cell carcinomas of the larynx

“…Ep‐CAM detection allows very small numbers of metastatic cells from head and neck carcinomas to be identified in bone marrow and sentinel lymph nodes . Ep‐CAM has been chosen as a reliable target for immunotherapy‐based treatments . However, studies of the participation of Ep‐CAM in the development of metastases from head and neck carcinomas have yielded controversial results: whereas Ep‐CAM expression is lower in metastases than in primary tumours, suggesting that the loss of Ep‐CAM favours metastasis, tumours with high scores of Ep‐CAM have the highest rate of metastasis .…”

“…10 Ep-CAM has been chosen as a reliable target for immunotherapy-based treatments. 11 However, studies of the participation of Ep-CAM in the development of metastases from head and neck carcinomas have yielded controversial results: whereas Ep-CAM expression is lower in metastases than in primary tumours, suggesting that the loss of Ep-CAM favours metastasis, 12 tumours with high scores of Ep-CAM have the highest rate of metastasis. 13 These controversies are discussed in detail by van der Gun et al 7 The monoclonal antibody E48 was developed originally for the detection and eradication of minimal residual disease in patients with head and neck SCC.…”

Head and neck cancer: a step forward

“…Th e epithelial cellular adhesion molecule (EpCAM) has been found to be overexpressed in HNSCC and therapeutic strategies are currently under clinical investigation [59,60]. Table 2 summarizes available medical treatment options for diff erent subgroups of patients with head and neck cancer.…”