Jean-Louis Pujol1, Johan F Vansteenkiste, Tommaso Martino De Pas, Djordje Atanackovic, Martin Reck, Michiel Thomeer, Jean-Yves Douillard, Gianpiero Fasola, Vanessa Potter, Paul Taylor, Lionel Bosquée, Robert Scheubel, Silvija Jarnjak, Muriel Debois, Pedro de Sousa Alves, Jamila Louahed, Vincent G Brichard, Frédéric F Lehmann. 1. *Thoracic Oncology Unit, Arnaud de Villeneuve Hospital/CHRU Montpellier, Montpellier, France; †Department of Pneumology, University Hospital, KU Leuven, Leuven, Belgium; ‡Medical Oncology, European Institute of Oncology, Milan, Italy; §Division of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute, Salt Lake City, Utah; ¶Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany; ‖Department of Respiratory Medicine, Ziekenhuis Oost Limburg, Genk and LCRP Oncology Cluster, University of Hasselt, Hasselt, Belgium; #Department of Medical Oncologie, ICO R. Gauducheau, St-Herblain, France; **Department of Oncology, University Hospital S. Maria della misericordia, Udine, Italy; ††Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; ‡‡Northwest Lung Centre, University Hospitals of South Manchester, Manchester, United Kingdom; §§Thoracic Oncology-Pneumology Service, André Renard Clinic, Herstal, Belgium; ¶¶Clinic of Thoracic Surgery, Waldburg-Zeil Clinic, Wangen im Allgäu, Germany; and ‖‖GSK Vaccines, Rixensart, Belgium.
Abstract
INTRODUCTION: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy. METHODS: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 μg recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4). RESULTS: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4 T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8 T-cell responses were only detected in four patients. CONCLUSION: In resected and unresectable NSCLC patients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses.
INTRODUCTION: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy. METHODS: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 μg recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4). RESULTS: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4 T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8 T-cell responses were only detected in four patients. CONCLUSION: In resected and unresectable NSCLCpatients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses.
Authors: Mary Zhang; Julie A Hong; Tricia F Kunst; Colleen D Bond; Cara M Kenney; Cheryl L Warga; Javier Yeray; Min-Jung Lee; Akira Yuno; Sunmin Lee; Markku Miettinen; R Taylor Ripley; Chuong D Hoang; Sacha Gnjatic; Jane B Trepel; David S Schrump Journal: Transl Lung Cancer Res Date: 2021-07
Authors: M Higgins; G Curigliano; V Dieras; S Kuemmel; G Kunz; P A Fasching; M Campone; T Bachelot; P Krivorotko; S Chan; A Ferro; L Schwartzberg; M Gillet; P M De Sousa Alves; V Wascotte; F F Lehmann; P Goss Journal: Breast Cancer Res Treat Date: 2017-02-07 Impact factor: 4.872