title: 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.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: *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.
authors: Jean-Louis
authors: JL
authors: Pujol
authors: Johan F
authors: JF
authors: Vansteenkiste
authors: Tommaso Martino
authors: TM
authors: De Pas
authors: Djordje
authors: D
authors: Atanackovic
authors: Martin
authors: M
authors: Reck
authors: Michiel
authors: M
authors: Thomeer
authors: Jean-Yves
authors: JY
authors: Douillard
authors: Gianpiero
authors: G
authors: Fasola
authors: Vanessa
authors: V
authors: Potter
authors: Paul
authors: P
authors: Taylor
authors: Lionel
authors: L
authors: Bosquée
authors: Robert
authors: R
authors: Scheubel
authors: Silvija
authors: S
authors: Jarnjak
authors: Muriel
authors: M
authors: Debois
authors: Pedro
authors: P
authors: de Sousa Alves
authors: Jamila
authors: J
authors: Louahed
authors: Vincent G
authors: VG
authors: Brichard
authors: Frédéric F
authors: FF
authors: Lehmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine