- Email: [email protected]
II first-in-human MATINS trial in patients with advanced solid tumours
abstracts
Annals of Oncology
LBA28
Genomic landscape of entrectinib resistance from ctDNA analysis in STARTRK-2
R.C. Doebele1, R. Dziadziuszko2, A. Drilon3, A. Shaw4, J. Wolf5, A.F. Farago4, L. Dennis6, T. Riehl7, B. Simmons7, C. Wu7, C-W. Chang7, V. Choeurng7, T.R. Wilson7 1 Thoracic Oncology Research Initiative, University of Colorado Cancer Center, Aurora, CO, USA, 2Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, 3Early Drug Development and Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 4Department of Medicine, Division of Hematology/ Oncology, Massachusetts General Hospital, Boston, MA, USA, 5Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany, 6Product Development, Foundation Medicine, Cambridge, MA, USA, 7Product Development Oncology, Genentech Inc., South San Francisco, CA, USA Background: Entrectinib is a small molecule inhibitor of ROS1 and TRKA,B,C, with deep and durable responses observed in ROS1 fusion-positive NSCLC (ROS1þ) and NTRK1,2,3 fusion-positive solid tumours (NTRKþ). Despite clinically meaningful activity, progression on entrectinib eventually occurs. Understanding the mechanisms of resistance could inform subsequent new personalised therapeutic options in these patients. Methods: Blood samples were collected at baseline and at the time of progression from most patients in the NTRKþ and ROS1þ patient populations enrolled on STARTRK-2 (NCT02568267). These were tested using the Foundation Medicine FoundationOne Liquid NGS-based test that assesses base substitutions, indels and rearrangements from 324 genes (including ROS1 and NTRK1,2,3), as well as copy number alterations from select genes using circulating tumour DNA (ctDNA) extracted from the plasma of patients from pre-treatment and following progression on entrectinib. Results: Of the 54 patients with NTRKþ tumours, 29 had paired samples at baseline and at progression at the time of data cut-off. Ten patients (34%) had a detectable NTRK solvent front mutation at disease progression (NTRK1: n ¼ 5; NTRK3: n ¼ 5), which were not detected in the pre-treatment sample. BRAF V600E and KRAS G12D mutations were detected at progression from a pancreatic cancer patient who had a partial response. Of the 53 patients with ROS1þ NSCLC, 18 had paired samples at baseline and at progression at the time of data cut-off. Four CD74-ROS1 and one SLC34A2ROS1 patients showed the emergence of an acquired ROS1 resistance mutation (G2032R and F2004C/I) at disease progression (28%), which were not present before treatment. One NRAS Q61K mutation was detected at the end of treatment collection sample from a patient who had a partial response. Conclusions: From blood analysis, acquired resistance mutations were detected in 34% of NTRKþ solid tumour and 28% of the ROS1þ NSCLC cohorts, all of which were mutations in the kinase domain of the oncogenic driver. One additional patient from
Volume 30 | Supplement 5 | October 2019
each cohort showed the emergence of a mutation in an oncogene within the MAPK pathway. Resistance to entrectinib can occur by multiple mechanisms, which should be studied in larger cohorts. Clinical trial identification: NCT02568267. Legal entity responsible for the study: F. Hoffman-La Roche. Funding: F. Hoffman-La Roche. Disclosure: R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain.; Research grant / Funding (self), Research grant / Funding (institution): Ignyta, Loxo, Mirati.; Licensing / Royalties: Abbott Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond.. R. Dziadziuszko: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, AstraZeneca, Pfizer, Novartis; Research grant / Funding (institution): Roche, Bristol-Myers Squibb, Merck, AstraZeneca, Pfizer, Novartis, Boehringer Ingelheim, Clovis; Travel / Accommodation / Expenses: Travels: Roche, AstraZeneca. A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health; Research grant / Funding (institution): Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar; Research grant / Funding (self): Foundation Medicine; Travel / Accommodation / Expenses: Merck - Food/Beverage, Puma - Food/ Beverage; Honoraria (self): Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice. A. Shaw : Honoraria (self), Advisory / Consultancy: ARIAD, Bayer, Blueprint Medicines, Chugai, Daiichi Sankyo, EMD Serono, Foundation Medicine, Genentech/ Roche, Guardant, Ignyta, KSQ Therapeutics, Natera, Novartis, Pfizer, Taiho Pharmaceutical, Takeda, and TP Therapeutics; Research grant / Funding (institution): Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, and TP Therapeutics. J. Wolf: Advisory / Consultancy, Officer / Board of Directors: AbbVie, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Chugai, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Takeda; Research grant / Funding (institution): BMS, Jannsen, MSD, Novartis, Pfizer. A.F. Farago: Research grant / Funding (institution): AstraZeneca, AbbVie, Genentech, BMS, Merck, PharmaMar, Amgen, Bayer, Loxo, Ignyta; Advisory / Consultancy: Genentech, Bayer, AbbVie, AstraZeneca, Boehringer Ingelheim, Loxo, PharmaMar. L. Dennis: Research grant / Funding (institution), Full / Part-time employment: Foundation Medicine. T. Riehl: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. B. Simmons: Full / Part-time employment: Roche. C. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. C. Chang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. V. Choeurng: Full / Part-time employment: Genentech, Inc. T.R. Wilson: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech.
LBA29
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 tumours
P. Bono1, M. Hollmen2, P. Jaakkola3, S. Shetty4, A. Thibault5, M.J.A. de Jonge6, A.R. Minchom7, Y.T. Ma4, C. Yap8, D. Robbrecht6, A. Pasanen3, S. Jalkanen2, R. Cruz5, A. Pal7, M.K. Karvonen9, J. Mandelin10, J. Koivunen11 1 Terveystalo Finland, Terveystalo Helsinki Kamppi, Helsinki, Finland, 2Medicity Research Laboratory, University of Turku, Turku, Finland, 3Comprehensive Cancer Center, Helsinki University Central Hospital (HUCH), Helsinki, Finland, 4Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK, 5Simbec-Orion, SimbecOrion Group Limited, Slough, UK, 6Erasmus University Medical Center, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, Netherlands, 7Drug Development Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, Sutton, UK, 8ICR Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK, 9 Medical, Faron Pharmaceuticals Ltd, Turku, Finland, 10Preclinical Development, Faron Pharmaceuticals Ltd, Turku, Finland, 11Department of Oncology, Oulu University Hospital, Oulu, Finland 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 CD8þ 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)
doi:10.1093/annonc/mdz394 | v865
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Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Sanofi. M. Chalabi: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Netherlands Cancer Institute. E.F. Smit: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (institution): Bayer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Research grant / Funding (institution): MSD; Honoraria (institution), Research grant / Funding (institution): Merck; Honoraria (institution): Novartis ; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution), Research grant / Funding (institution): Roche Genentech; Honoraria (institution): Seattle Genetics. N. Mehra: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Sanofi. E. Cuppen: Honoraria (institution), Advisory / Consultancy: Illumina; Honoraria (self), Advisory / Consultancy: InteRNA Technologies; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. H.M.W. Verheul: Honoraria (institution), Advisory / Consultancy: Glycostem; Honoraria (institution), Advisory / Consultancy: Lava Therapeutics. H. Gelderblom: Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Teva. All other authors have declared no conflicts of interest.
abstracts
v866 | Developmental therapeutics
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.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.018/5577815/ by guest on 08 October 2019
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 %), CD8þ/CD4þ 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). Legal entity responsible for the study: Faron Pharmaceuticals Ltd. Funding: Faron Pharmaceuticals Ltd.
Annals of Oncology
Annals of Oncology
LBA28
Genomic landscape of entrectinib resistance from ctDNA analysis in STARTRK-2
R.C. Doebele1, R. Dziadziuszko2, A. Drilon3, A. Shaw4, J. Wolf5, A.F. Farago4, L. Dennis6, T. Riehl7, B. Simmons7, C. Wu7, C-W. Chang7, V. Choeurng7, T.R. Wilson7 1 Thoracic Oncology Research Initiative, University of Colorado Cancer Center, Aurora, CO, USA, 2Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, 3Early Drug Development and Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 4Department of Medicine, Division of Hematology/ Oncology, Massachusetts General Hospital, Boston, MA, USA, 5Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany, 6Product Development, Foundation Medicine, Cambridge, MA, USA, 7Product Development Oncology, Genentech Inc., South San Francisco, CA, USA Background: Entrectinib is a small molecule inhibitor of ROS1 and TRKA,B,C, with deep and durable responses observed in ROS1 fusion-positive NSCLC (ROS1þ) and NTRK1,2,3 fusion-positive solid tumours (NTRKþ). Despite clinically meaningful activity, progression on entrectinib eventually occurs. Understanding the mechanisms of resistance could inform subsequent new personalised therapeutic options in these patients. Methods: Blood samples were collected at baseline and at the time of progression from most patients in the NTRKþ and ROS1þ patient populations enrolled on STARTRK-2 (NCT02568267). These were tested using the Foundation Medicine FoundationOne Liquid NGS-based test that assesses base substitutions, indels and rearrangements from 324 genes (including ROS1 and NTRK1,2,3), as well as copy number alterations from select genes using circulating tumour DNA (ctDNA) extracted from the plasma of patients from pre-treatment and following progression on entrectinib. Results: Of the 54 patients with NTRKþ tumours, 29 had paired samples at baseline and at progression at the time of data cut-off. Ten patients (34%) had a detectable NTRK solvent front mutation at disease progression (NTRK1: n ¼ 5; NTRK3: n ¼ 5), which were not detected in the pre-treatment sample. BRAF V600E and KRAS G12D mutations were detected at progression from a pancreatic cancer patient who had a partial response. Of the 53 patients with ROS1þ NSCLC, 18 had paired samples at baseline and at progression at the time of data cut-off. Four CD74-ROS1 and one SLC34A2ROS1 patients showed the emergence of an acquired ROS1 resistance mutation (G2032R and F2004C/I) at disease progression (28%), which were not present before treatment. One NRAS Q61K mutation was detected at the end of treatment collection sample from a patient who had a partial response. Conclusions: From blood analysis, acquired resistance mutations were detected in 34% of NTRKþ solid tumour and 28% of the ROS1þ NSCLC cohorts, all of which were mutations in the kinase domain of the oncogenic driver. One additional patient from
Volume 30 | Supplement 5 | October 2019
each cohort showed the emergence of a mutation in an oncogene within the MAPK pathway. Resistance to entrectinib can occur by multiple mechanisms, which should be studied in larger cohorts. Clinical trial identification: NCT02568267. Legal entity responsible for the study: F. Hoffman-La Roche. Funding: F. Hoffman-La Roche. Disclosure: R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain.; Research grant / Funding (self), Research grant / Funding (institution): Ignyta, Loxo, Mirati.; Licensing / Royalties: Abbott Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond.. R. Dziadziuszko: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, AstraZeneca, Pfizer, Novartis; Research grant / Funding (institution): Roche, Bristol-Myers Squibb, Merck, AstraZeneca, Pfizer, Novartis, Boehringer Ingelheim, Clovis; Travel / Accommodation / Expenses: Travels: Roche, AstraZeneca. A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health; Research grant / Funding (institution): Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar; Research grant / Funding (self): Foundation Medicine; Travel / Accommodation / Expenses: Merck - Food/Beverage, Puma - Food/ Beverage; Honoraria (self): Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice. A. Shaw : Honoraria (self), Advisory / Consultancy: ARIAD, Bayer, Blueprint Medicines, Chugai, Daiichi Sankyo, EMD Serono, Foundation Medicine, Genentech/ Roche, Guardant, Ignyta, KSQ Therapeutics, Natera, Novartis, Pfizer, Taiho Pharmaceutical, Takeda, and TP Therapeutics; Research grant / Funding (institution): Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, and TP Therapeutics. J. Wolf: Advisory / Consultancy, Officer / Board of Directors: AbbVie, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Chugai, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Takeda; Research grant / Funding (institution): BMS, Jannsen, MSD, Novartis, Pfizer. A.F. Farago: Research grant / Funding (institution): AstraZeneca, AbbVie, Genentech, BMS, Merck, PharmaMar, Amgen, Bayer, Loxo, Ignyta; Advisory / Consultancy: Genentech, Bayer, AbbVie, AstraZeneca, Boehringer Ingelheim, Loxo, PharmaMar. L. Dennis: Research grant / Funding (institution), Full / Part-time employment: Foundation Medicine. T. Riehl: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. B. Simmons: Full / Part-time employment: Roche. C. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. C. Chang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. V. Choeurng: Full / Part-time employment: Genentech, Inc. T.R. Wilson: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech.
LBA29
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 tumours
P. Bono1, M. Hollmen2, P. Jaakkola3, S. Shetty4, A. Thibault5, M.J.A. de Jonge6, A.R. Minchom7, Y.T. Ma4, C. Yap8, D. Robbrecht6, A. Pasanen3, S. Jalkanen2, R. Cruz5, A. Pal7, M.K. Karvonen9, J. Mandelin10, J. Koivunen11 1 Terveystalo Finland, Terveystalo Helsinki Kamppi, Helsinki, Finland, 2Medicity Research Laboratory, University of Turku, Turku, Finland, 3Comprehensive Cancer Center, Helsinki University Central Hospital (HUCH), Helsinki, Finland, 4Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK, 5Simbec-Orion, SimbecOrion Group Limited, Slough, UK, 6Erasmus University Medical Center, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, Netherlands, 7Drug Development Unit, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, Sutton, UK, 8ICR Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK, 9 Medical, Faron Pharmaceuticals Ltd, Turku, Finland, 10Preclinical Development, Faron Pharmaceuticals Ltd, Turku, Finland, 11Department of Oncology, Oulu University Hospital, Oulu, Finland 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 CD8þ 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)
doi:10.1093/annonc/mdz394 | v865
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Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Sanofi. M. Chalabi: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Netherlands Cancer Institute. E.F. Smit: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (institution): Bayer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Research grant / Funding (institution): MSD; Honoraria (institution), Research grant / Funding (institution): Merck; Honoraria (institution): Novartis ; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution), Research grant / Funding (institution): Roche Genentech; Honoraria (institution): Seattle Genetics. N. Mehra: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Sanofi. E. Cuppen: Honoraria (institution), Advisory / Consultancy: Illumina; Honoraria (self), Advisory / Consultancy: InteRNA Technologies; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. H.M.W. Verheul: Honoraria (institution), Advisory / Consultancy: Glycostem; Honoraria (institution), Advisory / Consultancy: Lava Therapeutics. H. Gelderblom: Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Teva. All other authors have declared no conflicts of interest.
abstracts
v866 | Developmental therapeutics
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.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.018/5577815/ by guest on 08 October 2019
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 %), CD8þ/CD4þ 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). Legal entity responsible for the study: Faron Pharmaceuticals Ltd. Funding: Faron Pharmaceuticals Ltd.
Annals of Oncology