Abstract 5335: The antigen target of IMGN901, CD56, is expressed at significant levels in merkel cell carcinoma (MCC)

Abstract

Abstract Background: IMGN901 consists of a CD56-binding monoclonal antibody, huN901, with a maytansinoid agent, DM1, attached via a stable disulfide linker, SPP. The CD56 antigen, also known as neural cell adhesion molecule (NCAM), is present in a number of malignancies including Merkel cell carcinoma (MCC), small cell lung carcinoma and other neuroendocrine tumors, ovarian cancers and multiple myeloma. Once bound to CD56, IMGN901 is internalized into a cancer cell and its DM1 is released to cause cell death via inhibition of tubulin polymerization. IMGN901 is currently in Phase I testing for the treatment of CD56-positive multiple myeloma and CD56-positive solid tumors. Six patients with MCC have received IMGN901, used as a single agent, in one of the Phase I trials underway. Clinical benefit was observed in 3 of these 6 patients: one complete response (CR), one partial response (PR) and one stable disease (SD). Objective: The goal of this study was to assess the potential utility of IMGN901 as a treatment for MCC by identifying the range of CD56 antigen expression levels in MCC. Methods: A calibrated immunohistochemical (IHC) staining method for CD56 was developed. CD56 staining conditions were established where 4 formalin fixed paraffin embedded (FFPE) MCC samples showed differential staining. FFPE cell pellet controls prepared from human tumor cell lines were next identified which showed CD56 staining in the same range as the MCC samples. The CD56 antigen level for each tumor cell line was subsequently quantified by flow cytometry. The calibrated IHC staining method was then applied to positive cell pellet controls and an extended panel of MCC tissues. For each resulting tissue section, the extent and intensity of immunostaining was evaluated and the CD56 expression level was estimated by comparing to the cell pellet controls. Results: The majority of samples from the MCC panel exhibited heterogeneous or homogeneous staining with significant levels of CD56 expression. Tissues from primary biopsy sites and from metastases showed comparable levels of CD56 expression. To date, biopsy samples have been acquired from 3 of the 6 MCC patients who have received IMGN901 (two IMGN901 non-responders and one responder) and these all showed high and homogeneous levels of CD56 expression. Conclusion: This IHC study indicates that the majority of MCC patient tissues express significant levels of CD56, supporting the development of the CD56-targeting compound, IMGN901, for this indication. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5335.