1024MO - A phase I/II MATINS trial: Part 1 pharmacokinetic, safety and efficacy results of Clever-1 blockade in advanced cancer

Background

Tumor associated macrophages (TAMs) have a pro-tumorigenic, anti-inflammatory M2 phenotype and express a scavenger receptor CLEVER-1 (Stabilin-1/FEEL-1). CLEVER-1 inhibition in mice reactivates CD8+ T-cell response with a robust anti-tumor activity. FP-1305 is a novel IgG4-antibody targeting CLEVER-1 and induces a phenotypic M2 to M1 immune switch of TAMs.

Methods

MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a three-part, first-in-human phase I/II study (NCT03733990) to assess the safety and preliminary efficacy of FP-1305 in patients with advanced solid tumours. The Part I has been completed. In Part II, 110 subjects with solid tumours will be enrolled for efficacy (ORR) and safety.

Results

In Part I, 30 patients were enrolled into five different dose levels (0.1 - 10 mg/kg) and received 1-8 doses (median 3) of FP-1305 q3w. FP-1305 was well tolerated without dose-limiting toxicities. 28.9 % of the treatment emergent adverse events were related to the study drug. The half-life of FP-1305 (t1/2) was 19.5 h (CV% 51.0). The disease control rate in target lesions was 27% and the overall response rate according to RECIST 1.1 was 3%. Peripheral increase in NK cells, CD4+, CD8+, CD8+/CD4+ T cells ratio, B cells and a decrease in regulatory T cells was observed after FP-1305 dosing. Also at least a 20 % increase of systemic IFNγ in 40 % of patients and CXCL10 in 33 % of patients was observed. FP-1305 dosing led to activation (CD25+) and Th1 skewing (CXCR3+) of T cell populations including increase in effector CD8 T-cell population with downregulation of several inhibitory immune checkpoint molecules (PD-1, PD-L1, CTLA-4 and LAG3). Data will be updated for PK and efficacy.

Conclusions

FP-1305 administration in advanced cancer patients can promote immune switch and peripheral lymphocyte activation alongside promising tolerability. Despite relatively short half-life, durable Th1 activation and mobilization of NK and B cells accompanied with persistent IFNγ and CXCL10 induction was observed. Despite formal progression according to RECIST, potential anti-tumour activity was noted with some target lesions showing regression or stability in several patients. Targeting Clever-1 holds promise as a novel immunotherapy.

Clinical trial identification

NCT03733990.

Editorial acknowledgement

Legal entity responsible for the study

Faron Pharmaceuticals LTD.

Funding

Faron Pharmaceuticals LTD.

Disclosure

P. Bono, P. Jaakkola, S. Shetty, Y.T. Ma, M.J.A. de Jonge, D. Robbrecht, A.R. Minchom, A. Pal, C. Yap, A. Pasanen, T. Skytta, A. Thibault, R. Cruz, J. Koivunen: Advisory/Consultancy: Faron Pharmaceuticals. M. Jalkanen: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Faron Pharmaceuticals LTD. S. Jalkanen: Advisory/Consultancy, Spouse/Financial dependant: Faron Pharmaceuticals LTD. M. Hollmén: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Faron Pharmaceuticals LTD. J. Mandelin, M. Karvonen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Faron Pharmaceuticals LTD.