PMID- 26309191 OWN - NLM STAT- MEDLINE DCOM- 20160915 LR - 20220420 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 10 IP - 10 DP - 2015 Oct TI - Safety and Immunogenicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive Non-Small-Cell Lung Cancer. PG - 1458-67 LID - 10.1097/JTO.0000000000000653 [doi] AB - 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 mug 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. FAU - Pujol, Jean-Louis AU - Pujol JL AD - *Thoracic Oncology Unit, Arnaud de Villeneuve Hospital/CHRU Montpellier, Montpellier, France; daggerDepartment of Pneumology, University Hospital, KU Leuven, Leuven, Belgium; double daggerMedical Oncology, European Institute of Oncology, Milan, Italy; section signDivision of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute, Salt Lake City, Utah; paragraph signDepartment 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; daggerdaggerNottingham University Hospitals NHS Trust, Nottingham, United Kingdom; double daggerdouble daggerNorthwest Lung Centre, University Hospitals of South Manchester, Manchester, United Kingdom; section sign section signThoracic Oncology-Pneumology Service, Andre Renard Clinic, Herstal, Belgium; paragraph sign paragraph signClinic of Thoracic Surgery, Waldburg-Zeil Clinic, Wangen im Allgau, Germany; and || ||GSK Vaccines, Rixensart, Belgium. FAU - Vansteenkiste, Johan F AU - Vansteenkiste JF FAU - De Pas, Tommaso Martino AU - De Pas TM FAU - Atanackovic, Djordje AU - Atanackovic D FAU - Reck, Martin AU - Reck M FAU - Thomeer, Michiel AU - Thomeer M FAU - Douillard, Jean-Yves AU - Douillard JY FAU - Fasola, Gianpiero AU - Fasola G FAU - Potter, Vanessa AU - Potter V FAU - Taylor, Paul AU - Taylor P FAU - Bosquee, Lionel AU - Bosquee L FAU - Scheubel, Robert AU - Scheubel R FAU - Jarnjak, Silvija AU - Jarnjak S FAU - Debois, Muriel AU - Debois M FAU - de Sousa Alves, Pedro AU - de Sousa Alves P FAU - Louahed, Jamila AU - Louahed J FAU - Brichard, Vincent G AU - Brichard VG FAU - Lehmann, Frederic F AU - Lehmann FF LA - eng SI - ClinicalTrials.gov/NCT00455572 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Antigens, Neoplasm) RN - 0 (MAGEA3 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Recombinant Proteins) RN - 5V9KLZ54CY (Vinblastine) RN - Q20Q21Q62J (Cisplatin) RN - Q6C979R91Y (Vinorelbine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antigens, Neoplasm/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/*therapy MH - Chemotherapy, Adjuvant MH - Cisplatin/administration & dosage MH - Cohort Studies MH - Female MH - Humans MH - Immunotherapy/methods MH - Lung Neoplasms/drug therapy/pathology/*therapy MH - Male MH - Middle Aged MH - Neoplasm Proteins/*therapeutic use MH - Neoplasm Staging MH - Recombinant Proteins/therapeutic use MH - Vinblastine/administration & dosage/analogs & derivatives MH - Vinorelbine EDAT- 2015/08/27 06:00 MHDA- 2016/09/16 06:00 CRDT- 2015/08/27 06:00 PHST- 2015/08/27 06:00 [entrez] PHST- 2015/08/27 06:00 [pubmed] PHST- 2016/09/16 06:00 [medline] AID - S1556-0864(15)33521-8 [pii] AID - 10.1097/JTO.0000000000000653 [doi] PST - ppublish SO - J Thorac Oncol. 2015 Oct;10(10):1458-67. doi: 10.1097/JTO.0000000000000653.