Abstract 4037: Optimizing the efficacy of anti-VEGF/cytotoxics/anti-PD-1 scheduling in a lung cancer mice model through B and T cells monitoring

Abstract The exact modalities of combinatorial regimens associating Immune Checkpoint Inhibitors (ICI) with other treatments are yet to be defined. Understanding how and when cytotoxics best reshape tumor immunity could help optimizing the scheduling of ICI’s. In vivo studies were performed on C57BL/6 mice grafted with LL/2lung cancer cells. A longitudinal immunomonitoring study on tumor, spleen and blood after multiple treatments including Cisplatin, Pemetrexed and anti-VEGF as single agents and in combination was performed for up to 21 days to determine the best time-window during which immune checkpoint inhibitors should be added. Finally, an efficacy study was conducted comparing the antiproliferative performance of various schedules of anti-VEGF, Pemetrexed-Cisplatin doublet, plus anti-PD-1 (i.e., immunomonitoring-guided scheduling, concurrent dosing or a random sequence). Immunomonitoring showed marked differences between treatments, organs and time-points. However, harnessing tumor immunity (i.e., promoting CD8 lymphocytes or increasing the CD8/Treg ratio) started on D7 and peaked on D14 with the anti-VEGF followed by cytotoxics combination. Therefore, a two-week delay between anti-VEGF/cytotoxic and anti-PD1 administration was considered the best sequence to test. Efficacy studies then confirmed that this sequence achieved higher anti-proliferative efficacy compared to other treatment modalities (i.e. -71% in tumor volume compared to control at the end of the study). Anti-VEGF and cytotoxic agents show time-dependent immunomodulatory effects, suggesting that sequencing is a critical feature when combining these agents with immune checkpoint inhibitors. Our efficacy study confirmed that sequencing treatments further enhances anti-proliferative effects in lung cancer models compared to concurrent dosing. Citation Format: Guillaume Sicard, Dorian Protzenko, Sarah Giacometti, Raphaelle Fanciullino, Fabrice Barlesi, Joseph Ciccolini. Optimizing the efficacy of anti-VEGF/cytotoxics/anti-PD-1 scheduling in a lung cancer mice model through B and T cells monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4037.