Jean-Pierre Delord1, Josep Tabernero2, Rocío García-Carbonero3, Andres Cervantes4, Carlos Gomez-Roca5, Yann Bergé1, Jaume Capdevila2, Luis Paz-Ares3, Desamparados Roda4, Paul Delmar6, David Oppenheim7, Sophia Soehrman Brossard6, Farzin Farzaneh7, Luigi Manenti8, Alexandre Passioukov8, Marion Gabriele Ott6, Jean-Charles Soria9. 1. Institut Claudius Regaud and Toulouse III University, Toulouse, France. 2. Vall d'Hebron University Hospital, VHIO, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Seville, Spain. 4. Department of Haematology and Medical Oncology, INCLIVA, University of Valencia, Spain. 5. Institut Gustave Roussy, Villejuif, France; University Paris South, France. 6. F. Hoffmann-La Roche Ltd., Basel, Switzerland. 7. Department of Haematological Medicine, King's College, London, UK. 8. Roche Glycart AG, Schlieren, Switzerland. 9. Institut Gustave Roussy, Villejuif, France; University Paris South, France. Electronic address: Jean-Charles.Soria@igr.fr.
Abstract
AIM: Imgatuzumab (GA201) is a novel anti-epidermal growth factor receptor (anti-EGFR) antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the efficacy of imgatuzumab in patients with EGFR-positive, KRAS-mutant advanced colorectal cancer. METHODS: Patients received single-agent imgatuzumab (1400mg on day 1 and 8 followed by q2W) as third line therapy in an open-label, multicentre, non-randomised, expansion study. The primary end-point was tumour response. Pre- and on-treatment biopsies and blood samples were investigated for biomarkers related to imgatuzumab's believed mechanism of action (MoA). RESULTS: 25 patients were treated and the best overall response was stable disease occurring in 40% of patients at 8weeks, 24% at 16weeks and 8% (two patients) at 32weeks. Median overall survival was 9.3months (95% confidence interval (CI): 5.1-12.3). Treatment-related rash, hypomagnesaemia and infusion-related reactions were the most common adverse events. Comparison of pre- and post-treatment biopsies revealed that the number of tumour-infiltrating immune cells increased notably after one cycle of therapy (median compound immune reactive score of 1491 versus 898 cells/mm(3) at baseline), whereas the number of peripheral natural killer cells decreased. A potential association between baseline tumour immune infiltration and clinical efficacy was seen. CONCLUSIONS: These data may suggest that the MoA of imgatuzumab involves ADCC-related immune effects in the tumour and is not limited to simple receptor blockade.
AIM: Imgatuzumab (GA201) is a novel anti-epidermal growth factor receptor (anti-EGFR) antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the efficacy of imgatuzumab in patients with EGFR-positive, KRAS-mutant advanced colorectal cancer. METHODS: Patients received single-agent imgatuzumab (1400mg on day 1 and 8 followed by q2W) as third line therapy in an open-label, multicentre, non-randomised, expansion study. The primary end-point was tumour response. Pre- and on-treatment biopsies and blood samples were investigated for biomarkers related to imgatuzumab's believed mechanism of action (MoA). RESULTS: 25 patients were treated and the best overall response was stable disease occurring in 40% of patients at 8weeks, 24% at 16weeks and 8% (two patients) at 32weeks. Median overall survival was 9.3months (95% confidence interval (CI): 5.1-12.3). Treatment-related rash, hypomagnesaemia and infusion-related reactions were the most common adverse events. Comparison of pre- and post-treatment biopsies revealed that the number of tumour-infiltrating immune cells increased notably after one cycle of therapy (median compound immune reactive score of 1491 versus 898 cells/mm(3) at baseline), whereas the number of peripheral natural killer cells decreased. A potential association between baseline tumour immune infiltration and clinical efficacy was seen. CONCLUSIONS: These data may suggest that the MoA of imgatuzumab involves ADCC-related immune effects in the tumour and is not limited to simple receptor blockade.
Authors: Maria Carmen Ochoa; Luna Minute; Inmaculada Rodriguez; Saray Garasa; Elisabeth Perez-Ruiz; Susana Inogés; Ignacio Melero; Pedro Berraondo Journal: Immunol Cell Biol Date: 2017-02-21 Impact factor: 5.126
Authors: S Temam; J Spicer; F Farzaneh; J C Soria; D Oppenheim; M McGurk; A Hollebecque; J Sarini; K Hussain; S Soehrman Brossard; L Manenti; S Evers; P Delmar; L Di Scala; C Mancao; F Feuerhake; L Andries; M G Ott; A Passioukov; J P Delord Journal: Ann Oncol Date: 2017-11-01 Impact factor: 32.976
Authors: John P Veluchamy; Nina Kok; Hans J van der Vliet; Henk M W Verheul; Tanja D de Gruijl; Jan Spanholtz Journal: Front Immunol Date: 2017-05-31 Impact factor: 7.561
Authors: Yu Imamura; Paul Lochhead; Mai Yamauchi; Aya Kuchiba; Zhi Rong Qian; Xiaoyun Liao; Reiko Nishihara; Seungyoun Jung; Kana Wu; Katsuhiko Nosho; Yaoyu E Wang; Shouyong Peng; Adam J Bass; Kevin M Haigis; Jeffrey A Meyerhardt; Andrew T Chan; Charles S Fuchs; Shuji Ogino Journal: Mol Cancer Date: 2014-05-31 Impact factor: 27.401
Authors: Martin Pool; Arjan Kol; Marjolijn N Lub-de Hooge; Christian A Gerdes; Steven de Jong; Elisabeth G E de Vries; Anton G T Terwisscha van Scheltinga Journal: Oncotarget Date: 2016-10-18