Promising clinical benefit rates in advanced cancers alongside potential biomarker correlation in a phase I/II trial investigating bexmarilimab, a novel macrophage-guided immunotherapy.

2645 Background: Clever-1 is an immunosuppressive scavenger receptor expressed on tumor associated macrophages. High levels of Clever-1 are associated with poor survival and immunotherapy resistance. Bexmarilimab (FP-1305) is a novel humanized anti-CLEVER-1 IgG4-antibody capable of inducing a phenotypic M2 to M1 immune switch of tumor-associated macrophages. Methods: MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a first-in-human phase I/II study (NCT03733990) to assess safety and preliminary efficacy of Bexmarilimab in patients with refractory advanced solid tumours. Part I has been completed with initial good safety profile of the IMP, preliminary signs of efficiency, and recommended dose of 1mg/kg Q3W for part II (ESMO 2020). In Part II (ESMO 2021), 10 distinct solid tumour types were enrolled to assess preliminary efficacy (overall survival (OS), progression free survival (PFS), and clinical benefit rate (CBR). Clever-1 IHC in pre-treatment biopsies with Ventana platform using a primary antibody 4G9 (Santa Cruz) was scored by % of positive cells compared to the viable tumor cells. Results: At the Jan 2022, a total of 193 patients have been enrolled to the study. In the completed cohorts, 138 patients have received 1-21 doses (median 3) of Bexmarilimab Q3W. Bexmarilimab was well tolerated, and no new safety signals were detected. Part I and Part II fully enrolled 11 cancer cohorts, the median PFS was 2.0 months (95% CI 1.9 – 2.0) and the median OS was 5.2 months (95% CI 4.3 – 6.4). CBR for Part II was 17.3% (19/110) at cycle 4 of treatment (by RECIST v.1.1). Notably, 30-40% CBR at cycle 4 was seen in cutaneous melanoma (30%), gastric cancer (30%), cholangiocarcinoma (30%), hepatocellular cancer (40%), and ER+ breast cancer (40%). Six-month survival rates (landmark analysis) were 70.1% for CBR compared to 34.7% for non-CBR patients, with a similar duration of prior therapy in both groups. Preliminary biomarker analysis (n = 77) demonstrated positive trend (p = 0.038) between CBR and higher intratumoral Clever-1 positivity (median of 15% positivity (range 0-25) in CBR and 3% (range 0-85) in non-CBR patients) Conclusions: Bexmarilimab continues to demonstrate promising anti-tumour activity as a monotherapy in several refractory solid tumours. Furthermore, preliminary biomarker analysis suggests a possibility for patient selection based on tumour Clever-1 expression. Further expansion of the study will investigate optimal dosing and biomarkers of efficacy. Clinical trial information: NCT03733990.