Abstract 4974: Q702, selective Axl/Mer/CSF1R triple kinase inhibitor enhance the activity of immune checkpoint inhibitor by alteration of immunosuppressive tumor microenvironment

Abstract

Abstract Central to the Immune Checkpoint Inhibitors (ICI) mechanism is the activation and infiltration of the cytotoxic CD8+ T cells following tumor-antigen recognition. However, the effector functions of the CD8+ T cells can be highly compromised by immunosuppressive tumor microenvironment (TME). There is the growing appreciation of the potential contributions of innate immune modulation to antitumor immunity which suggests the need for the novel strategies to elicit a more efficient/robust immune response against malignant cells. Axl/Mer/CSF1R play vital roles in the immunosuppressive TME by increasing regulatory T cell, M2 macrophage, myeloid-derived suppression cell (MDSC) and suppressing antigen presentation. Previously, we have reported a novel selective Axl/Mer/CSF1R kinase inhibitor, Q702 and demonstrated tumor regression by alteration of the immunosuppressive TME. We present the anti-tumor efficacy and immune mechanism of Q702 in combination with anti-PD-1 in the various syngeneic models. The combination of Q702 and anti-PD-1 demonstrated tumor regression through enhanced tumor infiltration of effector immune cells, altered cytokine expression promoting promoted tumor specific antigen presentation and unregulated PD-L1 expression on tumor cells. Additionally, the Q702 alone induced tumor regression in the anti-PD-1 non-responding syngeneic models. These results suggest that the innate immune modulation in the TME by Q702 in combination with an ICI can be through synergistic mechanisms of action. In addition, the data suggests that Q702 could potentially broaden the patient population that benefits from ICI-based immunotherapy. Q702 is progressing through IND-enabling studies to support initiation of a Phase 1 oncology clinical study in early 2020. Citation Format: Yeong-In Yang, Hwankyu Kang, Dongsik Park, Yeejin Jeon, Jeongjun Kim, Baejung Choi, Jaeseung Kim, Kiyean Nam. Q702, selective Axl/Mer/CSF1R triple kinase inhibitor enhance the activity of immune checkpoint inhibitor by alteration of immunosuppressive tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4974.