Abstract 2266: Efficacy of CEACAM1-targeting immunoglobulin in combination with pembrolizumab in lung cancer
Authors: Jae-Hwan Kim, Kyoung-Ho Pyo, Min-Jee Jung, Minkyu Hur, Jonghwa Won, Byoung Chul Cho
Journal: Cancer Research (2019)

Abstract Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as an immune check point molecule is expressed in lung cancer cells. The homophilic interaction of CEACAM1 inhibits killing effect of T cells by co-inhibitory signal transduction. Thus, up-regulated CEACAM1 in the tumor microenvironment is considered as a promising therapeutic target for cancer. In this study, anti-cancer effect of anti-CEACAM1 monoclonal antibody (MG1124, from GC Pharma, Yongin, South Korea) was investigated with lung cancer-xenograft humanized mice. Materials &amp; Methods: Multispectral image analysis using Vectra polaris system was performed in 49 of human lung cancers (36 adenocarcinoma; 13 squamous cell carcinoma) to evaluate the expressions of CEACAM1, PD-L1 and CD8. Four tumors (YHIM-01, YHIM-02, YHIM-03 and YHIM-04) with high CEACAM1 expression were subcutaneously implanted into humanized mice (hu-CD34 NSG) matched with HLA-A. Efficacy of MG1124 was performed by the single mouse trial format. Humanized mice were treated with MG1124 (q2w, 20 mpk, i.p. injection) with or without pembrolizumab (q2w, 10 mpk, i.p. injection). Findings: Among 49 lung cancers evaluated, proportion of tumor cells expressing CEACAM1 and PD-L1 with any intensity ranged 0.1- 89.2% (median, 15.4%) and 0.2% - 95.6% (median, 6.8%) respectively, and TIL counts ranged 0 - 1,200 cells/mm2 (median, 129 cells/mm2). Four tumors with high CEACAM1(14.5% in YHIM-01, 81.2% in YHIM-02, 23.8% in YHIM-03 and 36.7% in YHIM-04) were selected to establish humanized mouse models. MG1124 as a monotherapy demonstrated antitumor activity and also was superior to pembrolizumab in 1 (YHIM-02, TGI=63.4±1.7% for combination vs. TGI=58.7±9.1% for pembrolizumab alone) out of 4 humanized mouse models. Combination of MG1124 with pembrolizumab also demonstrated synergic anti-tumor effect in 3 models (YHIM-01, TGI= 39.6±19.7% vs. 0.6±11.4% for pembrolizumab alone, vs. 16.5±33.3% for MG1124 alone; YHIM-02, TGI=58.7±9.1% vs. 38.2±14.9% for pembrolizumab, vs. 63.4±1.7% for MG1124 alone; YHIM-03, TGI= 35.6±13.2% vs. TGI=0.0±13.2% for pembrolizumab alone, vs. TGI=3.1±13.3% for MG1124 alone). PD-L1 expression was not associated with MG1124 alone or in combination with pembrolizumab (PD-L1, 2.5% in YHIM-01, 0.5% in YHIM-02 and 14.0% in YHIM-03 respectively). Interestingly, however, combinational effects of MG1124 and pembrolizumab were shown only in 3 models showing high CD8+ T cell infiltration in the tumors (209, 432, 362 vs. 46 in a model without combination synergy). Conclusion: CEACAM1-targeting monoclonal antibody, MG1124, exhibits promising anti-cancer effects in CEACAM1-expressing lung cancers. Tumoral CEACAM1 expression and high intratumoral CD8+ T cell infiltration could serve as a predictive biomarker to MG1124 monotherapy or in combination with pembrolizumab and need to be further investigated. Citation Format: Jae-Hwan Kim, Kyoung-Ho Pyo, Min-Jee Jung, Minkyu Hur, Jonghwa Won, Byoung Chul Cho. Efficacy of CEACAM1-targeting immunoglobulin in combination with pembrolizumab in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2266.