Abstract 1313P
Background
CEACAM5 is a cell surface biomarker protein with high expression in NSCLC. Tusamitamab ravtansine (tusa; SAR408701) consists of an antibody-drug conjugate of a humanized CEACAM5-specific monoclonal antibody linked to DM4, a potent anti-tubulin agent. In a phase I/II study (NCT02187848), tusa showed antitumor activity in pretreated pts with advanced non-squamous NSCLC and high CEACAM5 expression. Here, we report CEACAM5 expression levels, patterns, and correlation with demographic variables in these pts.
Methods
CEACAM5 expression was assessed using available archival tumor samples and analyzed locally at clinical sites and/or centrally in a laboratory by immunohistochemistry using murine anti-CEACAM5 clone 769. High expression was defined as ≥ 50% of tumor cells per specimen with CEACAM5 positive staining at ≥ 2+ intensity; moderate expression was ≥ 1 to < 50% of tumor cells at ≥ 2+ intensity. CEACAM5 staining may exhibit a polarized (partial apical or basolateral) or whole (complete or partial) membrane pattern. CEACAM5 correlation with demographic variables was analyzed.
Results
Among 888 prescreened pts, 19.4% had high CEACAM5 expression and 23.6% had moderate expression. For high CEACAM5 expressors recruited in the study (N = 64), CEACAM5 staining was observed over the whole membrane (mean percentage of CEACAM5 positive cells at ≥ 2+ intensity = 51.95%) or was polarized (25.08%). Among CEACAM5 moderate expressors recruited (N = 28), mean percentage of CEACAM5 positive cells was 6.96% for whole membrane staining and 6.89% for polarized staining. No correlations were noted between CEACAM5 expression and pt sex, age, race, or ethnicity for either CEACAM5 high or moderate expressors.
Conclusions
Almost 20% of prescreened NSCLC pts had high CEACAM5 expression. High CEACAM5 expressors exhibited a mixed pattern of whole membrane and polarized staining, with a predominance of whole membrane expression. In CEACAM5 moderate expressors, whole membrane CEACAM5 expression was similar to polarized CEACAM5 expression. CEACAM5 expression was not correlated with demographic variables.
Clinical trial identification
NCT02187848.
Editorial acknowledgement
Editorial support was provided by Amanda Sheldon, PhD of inScience Communications (Philadelphia, PA, USA), funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
A. Bauchet: Financial Interests, Personal, Full or part-time Employment: Sanofi. J. Adam: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Research Grant: MSD. P. Nuciforo: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Research Grant: Bayer. F. López-Rios: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Thermo Fisher; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Thermo Fisher; Financial Interests, Institutional, Research Grant: Pfizer. C. Henry: Financial Interests, Personal, Full or part-time Employment: Sanofi. M. Ozoux: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. All other authors have declared no conflicts of interest.