694P - Full efficacy analysis of phase I/II trial investigating bexmarilimab, a novel macrophage-guided immunotherapy in refractory solid tumors

Background

Clever-1 is an immunosuppressive scavenger receptor expressed on tumor associated macrophages. Bexmarilimab (FP-1305) is a novel humanized anti-CLEVER-1 IgG4-antibody capable of switching tumor macrophage phenotype leading to T-cell mediated anti-tumor responses.

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 (Bex) in patients with refractory advanced solid tumours. Part I has been completed with initial adequate safety profile, preliminary signs of efficacy, and initial recommended dose of 1mg/kg Q3W for part II. In Part II, 10 patients with distinct solid tumour types and variable doses and dosing frequency of Bex were studied to investigate safety, tolerability and efficacy.

Results

At the data cut-off of Apr 17th 2023, 214 patients have been enrolled to the study. In the alternative dosing cohorts, 66 patients were exposed to Bex with 1-3mg/kg Q1W, 1-3mg/kg Q2W, or 3-30mg/kg Q3W dosing. Bex was well tolerated with fatigue (15.9%) and pyrexia (5.6%) being the most frequent treatment related adverse event (TRAE) and 7.9% of the patients experiencing grade 3-4 TRAE. Disease control rate (DCR) was 13.0% (n=28) overall. Highest disease control rates (DCR) were observed in hepatocellular cancer (36%), ER+ breast cancer (33%), cutaneous melanoma (22%), and cholangiocarcinoma (21%). DCR was associated with Bex-induced immune activation in blood and tumor. Median progression-free survival was 2.0 and overall survival 5.6 months. 18-month survival rates (landmark analysis) were 32.9% in patients achieving DCR while this was 5.5% in non-DCR patients. The PFS ratio (defined by the PFS on bex/duration of previous treatment line) was > 1.3 in 46.4% of the DCR patients while this was 9.6% in non-DCR patients (p<0.0001). In the alternative dosing regimens, no dose-dependency was observed to adverse events or DCR rates.

Conclusions

Bexmarilimab demonstrates promising anti-tumour activity as a monotherapy in several refractory solid tumours. A dose of 1mg/kg Q3W is considered feasible for further monotherapy studies in solid tumors.

Clinical trial identification

NCT03733990.

Editorial acknowledgement

Legal entity responsible for the study

Faron Pharmaceuticals.

Funding

Faron Pharmaceuticals.

Disclosure

P. Bono: Financial Interests, Personal, Advisory Board: MSD, Oncorena, TILT Biotherapeutics, Faron Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, Chief Medical Officer: Terveystalo Finland; Financial Interests, Personal, Stocks/Shares: Terveystalo Finland; Financial Interests, Personal, Ownership Interest: TILT Biotherapeutics; Other, Stock ownership (spouse): Faron Pharmaceuticals. L. Verlingue: Financial Interests, Personal, Stocks/Shares, CEO of Resolved dedicated to treatment approval prediction: Resolved; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Contract for bioinformatic analysis: Pierre Fabre, Servier; Non-Financial Interests, Advisory Role: Klineo; Non-Financial Interests, Institutional, Proprietary Information, As part of the Drug Development Department (DITEP) of Gustave Roussy and of the Phase 1 unit of Centre Léon Bérard, as medical doctor, LV report being: Principal/sub-Investigator of Clinical Trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd., Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, F. Hoffmann-La Roche AG, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma A: Pharmas. M.J. De Miguel Luken: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, BioNTech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. A. Pasanen: Financial Interests, Personal, Advisory Board: Gilead, Roche, Novartis, Varian, Incyte; Financial Interests, Personal, Invited Speaker: Roche, Janssen-Cilag, Incyte; Non-Financial Interests, Principal Investigator: Faron, Incyte. D. Robbrecht: Financial Interests, Personal, Advisory Board: Merck AG, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Treatmeds, DUOS; Non-Financial Interests, Advisory Role: Bayer; Non-Financial Interests, Principal Investigator: Sanofi, Incyte, Roche, InteRNA, Numab Therapeutics, Menarini. T. Skyttä: Financial Interests, Personal, Invited Speaker: BMS, AstraZeneca; Financial Interests, Personal, Other, DMC: Faron; Financial Interests, Personal, Advisory Board: Novartis, Pierre Fabre, MSD; Financial Interests, Personal, Member of Board of Directors: Finnish Oncological Society. S.M.E. Iivanainen: Financial Interests, Personal, Advisory Board: MSD, BMS, Novartis, Roche; Financial Interests, Institutional, Invited Speaker: BMS, Faron; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Institutional, Other, Sub-investigator: MSD; Financial Interests, Personal and Institutional, Invited Speaker, The Origama study: Roche; Financial Interests, Institutional, Other, Sub-Investigator (The ECHO Trial): Kaiku Health; Other, Study Steering Committee Member: F. Hoffmann-La Roche. S. Shetty: Financial Interests, Personal, Other, Consultancy fees: Faron Pharmaceuticals; Financial Interests, Personal, Invited Speaker, Speaker fees for educational event: Eisai; Non-Financial Interests, Principal Investigator, UK coordinating investigator: Faron Pharmaceuticals. Y.T. Ma: Financial Interests, Personal, Advisory Board: Eisai, Roche, AstraZeneca, Ipsen; Financial Interests, Personal, Steering Committee Member: Faron; Financial Interests, Institutional, Local PI: Faron; Financial Interests, Institutional, Coordinating PI: QED. D.M. Graham: Financial Interests, Personal, Advisory Board, Consulting role on advisory board: clinigen; Financial Interests, Personal, Invited Speaker: Cancer Drug Development Fund; Financial Interests, Personal, Advisory Board: McCann Health; Financial Interests, Institutional, Invited Speaker, Institutional funding from study: MSD, Codiak Biosciences, Starpharma, Faron Pharmaceuticals, Synthon, Janssen; Financial Interests, Institutional, Other, Sub-I: Institutional funding from study: AstraZeneca, Roche, BerGenBio, GSK, Bayer, Bicycle pharmaceuticals, Carrick, Taiho pharmaceuticals, CytomX Therapeutics, RedX Pharma PLC, Eisai Inc, Octimet, Orion Pharma, Kinex pharmaceuticals, Boehringer Ingelheim, BMS, Turning Point Therapeutics, Immutep, Agalimmune, Kymab, Blueprint, Astellas, Cellcentric, UCB Biopharma USL, Eli Lily, Seagen, Repare therapeutics, Timepoint Therapeutics, Astex, Stemline, Crescendo Biologics Ltd., ADC Therapeutics, Genentech, Avacta Life Sciences Ltd., Nurix Therapeutics Inc; Financial Interests, Institutional, Other, Sub-I: Institutional finding from study: Chugai Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: Incyte. S.P. Arora: Financial Interests, Personal, Invited Speaker: Exelixis, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: QED Therapeutics, AstraZeneca, Seagen; Financial Interests, Institutional, Local PI: Caris Life Sciences, Faron, Isofol, Ipsen, BeiGene, Tvardi, Novartis, Therabionic, Genentech; Non-Financial Interests, Member of Board of Directors: Support New India. P.M. Jaakkola: Financial Interests, Personal, Advisory Board: MSD, Ipsen. C. Yap: Financial Interests, Personal, Advisory Board, Statistical Consultant: Faron Pharmaceutical; Financial Interests, Personal, Invited Speaker, Speaker at a Training Workshop: Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis; Financial Interests, Personal and Institutional, Research Grant: Faron Pharmaceuticals. M. Hollmén: Financial Interests, Personal, Full or part-time Employment, Chief Scientific Officer: Faron Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Invited Speaker, Research agreement for the pre-clinical and clinical development of bexmarilimab: Faron Pharmaceuticals; Non-Financial Interests, Personal, Product Samples, Bexmarilimab (anti-Clever-1 antibody) and MATINS clinical trial patient material: Faron Pharmaceuticals. J.P. Koivunen: Financial Interests, Personal, Advisory Board: Merck Sharp Dome, BMS, AstraZeneca, Pfizer, Roche, Boehringer-Ingelheim, Takeda, Amgen; Financial Interests, Personal, Full or part-time Employment: Faron Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim, Roche. A.R. Minchom: Financial Interests, Personal, Other, Expenses: Amgen pharmaceuticals, Loxo Oncology; Financial Interests, Personal, Invited Speaker: Bayer Pharmaceuticals, Chugai Pharmaceuticls, GSK, Janssen Pharmaceuticals, Merck pharmaceuticals; Financial Interests, Personal, Advisory Board: Faron pharmaceuticals, Janssen Pharmaceuticals, Merck pharmaceuticals, Takeda, Genmab; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Institutional, Other, Research funding: MSD, Merck Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Novartis Oncology.