6587 - Immune activation with a novel immune switch anti-macrophage antibody (anti-Clever-1 mAb; FP-1305) in phase I/II first-in-human MATINS trial in patients with advanced solid tumors

Background

CLEVER-1 is a scavenger receptor that is highly expressed on tumor associated macrophages (TAMs) and mediates the clearance of “unwanted” self-components. Pre-clinical studies demonstrate that CLEVER-1 inhibition switches TAMs to a pro-inflammatory phenotype and reactivates CD8+ T-cell responses with a robust anti-tumour activity (Viitala et al. Clin Cancer Res 2019). Targeting CLEVER-1 could overcome the immunosuppressive tumour microenvironment and has led to the development of FP-1305, a humanized anti-CLEVER-1 IgG4-antibody.

Methods

MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a multicenter first-in-human phase I/II study (NCT03733990) to assess the tolerability, safety and preliminary efficacy of FP-1305 in patients (pts) with advanced, IO-refractory melanoma, cholangiocarcinoma, hepatocellular, colorectal, and pancreatic ductal adenocarcinoma (PDAC)

Results

11 pts (median age 57) were enrolled in four cohorts (0.3, 1.0, 3.0 or 10 mg/kg) and received 1-8 cycles (median 3) of FP-1305 every three weeks. FP-1305 has been well tolerated without dose-limiting toxicities. Most frequent treatment-emergent adverse events (AEs; ≥20%) were fatigue and raised ALT and AST levels. Initial FP-1305 dosing led to an increase in blood NK cells (median 154 %), CD8+/CD4+ T cell ratio (median 121 %), B cells (median 143 %) and a decrease in regulatory T cells (median 65 % from baseline). Clinical benefits have been observed in two colorectal cancer pts. One with an ongoing partial response (-52%) and another with disease stabilization along with a decline in Carcinoembryonic antigen (CEA). The updated safety and efficacy results will be reported.

Conclusions

FP-1305 is the first macrophage checkpoint candidate promoting immune switch with promising tolerability and clinical anti-tumor activity. Analysis of circulating immune cells after administration of FP-1305 demonstrates Th1 activation as well as mobilization of NK cells and B cells.

Clinical trial identification

EudraCT: 2018-002732-24 (obtained 09 Jul 2018).

Editorial acknowledgement

Legal entity responsible for the study

Faron Pharmaceuticals Ltd.

Funding

Faron Pharmaceuticals Ltd.

Disclosure

P. Bono: Full / Part-time employment, Employment: Terveystalo; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Stock owenership and Scientific Board member: TILT Biotherapeutics; Spouse / Financial dependant, Family member’s stock ownereship: Faron pharmaceuticals; Advisory / Consultancy: Faron pharmaceuticals; Advisory / Consultancy, Scientific Board member: Oncorena; Advisory / Consultancy: Pfizer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Orion Pharma; Advisory / Consultancy: Ipsen ; Honoraria (self), Data safety monitoring Board member: Herantis Pharma. M. Hollmen: Advisory / Consultancy, Shareholder / Stockholder / Stock options, patent holder: faron pharmaceuticals. P. Jaakkola: Advisory / Consultancy: Faron Pharmaceuticals. S. Shetty: Advisory / Consultancy: Faron Pharmaceuticals. A. Thibault: Full / Part-time employment: Simbec-Orion. M.J.A. de Jonge: Advisory / Consultancy: Faron Pharmaceuticals. A.R. Minchom: Advisory / Consultancy: Faron Pharmaceuticals. Y.T. Ma: Advisory / Consultancy: Faron Pharmaceuticals. C. Yap: Advisory / Consultancy: Faron Pharmaceuticals. D. Robbrecht: Advisory / Consultancy: Faron Pharmaceuticals. S. Jalkanen: Shareholder / Stockholder / Stock options: Faron Pharmaceuticals. M.K. Karvonen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Mandelin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Koivunen: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneza; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: KaikuHealth; Research grant / Funding (self): Roche. All other authors have declared no conflicts of interest.