Introduction: Bexmarilimab is a novel macrophage re-programming agent targeting CLEVER-1 on tumor associated macrophages. CLEVER-1 is a highly immunosuppressive macrophage scavenger receptor. Inhibition of CLEVER-1 has been shown remove T cell exhaustion, induce clonal expansion of cytotoxic CD8 cells, and improve their infiltration into the tumor. Recently in a first-in-human Phase I/II study named MATINS (NCT03733990) bexmarilimab was reported to have a survival benefit in 30% of patients with advanced gastric cancer, cutaneous melanoma and cholangiocarcinoma as a single agent (ESMO 2021).

Methods & Aims: As a part of the mode of action of bexmarilimab, it is known to induce TNFa and IFNg responses, especially when IFNg levels are low. Using ROC analysis we aimed to test the performance of baseline cytokine serum IFNg and TNFa levels to identify patients that experienced a survival benefit from bexmarilimab compared to patients that did not benefit from bexmarilimab.

Results: 30 patients, 10 per each tumor type, were treated with bexmarilimab at 1mg/kg Q3W. Mean age 59 years (SD, 9 years), 73% male, with an average of 3 previous lines of therapy, median survival not yet reached. At baseline, patients that saw a clinical benefit (CBR) from bexmarilimab had average serum IFNg levels of 5.11 pg/ml (SD, +/- 4.99 pg/ml) compared to 13.07 pg/ml (SD, +/- 13.26) in patients that did not respond to the treatment. Similarly serum TNFa levels 0.96 pg/ml (SD, +/- 0.74 pg/ml) in patients that benefited from bexmarilimab compared to 2.37 pg/ml (SD, +/- 1.43 pg/ml) in patients that did not respond to the treatment. Log transformed values were used for ROC analyses. Used together IFNg and TNFa performed well to identify patients that are responsive to bexmarilimab (AUC 0.83, P < 0.0001).

Conclusion: Bexmarilimab works well in patients with low IFNg and TNFa levels, which is opposite to what is usually seen with checkpoint inhibitors and other T cell activating agents.

Citation Format: Jussi Koivunen, Juho Jalkanen, Mari Björkman, Jami Mandelin, Petri Bono. Low baseline serum IFNg and TNFa are predictive of response to bexmarilimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2767.