1173O - MAGRIT, a double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of the recMAGE-A3 + AS15 cancer immunotherapeutic as...

Date 28 September 2014
Event ESMO 2014
Session Presidential Symposium 1
Topics Non-Small-Cell Lung Cancer, Early Stage
Cancer Immunology and Immunotherapy
Presenter Johan Vansteenkiste
Citation Annals of Oncology (2014) 25 (suppl_4): iv409-iv416. 10.1093/annonc/mdu347
Authors J.F. Vansteenkiste1, B. Cho2, T. Vanakesa3, T. De Pas4, M. Zielinski5, M.S. Kim6, J. Jassem7, M. Yoshimura8, J. Dahabreh9, H. Nakayama10, L. Havel11, H. Kondo12, T. Mitsudomi13, K. Zarogoulidis14, O.A. Gladkov15, B. Spiessens16, V. Brichard16, C. Debruyne16, P. Therasse17, N.K. Altorki18
  • 1Respiratory Oncology Unit (pulmonology), University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 2Division Of Oncology, Department Of Internal Medicine, Yonsei University, College of Medicine, 120-752 - Seoul/KR
  • 3Cardiothoracic Surgery Network, North Estonian Medical Center, 11345 - Tallinn/EE
  • 4Servizi Oncologici, Istituto Europeo di Oncologia, IT-20141 - Milano/IT
  • 5Thoracic Surgery, Pulmonary Hospital Zakopane, 34500 - Zakopane/PL
  • 6Center For Lung Cancer, National Cancer Center, 410-769 - Goyang/KR
  • 7Oncology And Radiotherapy, Medical University of Gdansk, PL-80-211 - Gdansk/PL
  • 8Thoracic Surgery, Hyogo Cancer Center, 673-8558 - Akashi/JP
  • 9Athens Medical Center, Thoracic Surgery Department, 15125 - Athens/GR
  • 10Thoracic Oncology, Kanagawa Cancer Center Hospital, 8515 - Yokohama/JP
  • 11Dept Of Pneumonology And Thoracic Surgery, Fakultni Nemocnice Na Bulovce, 18081 - Prague /CZ
  • 12General Thoracic Surgery, Kyorin University, School of Medicine, 181-8611 - Tokyo/JP
  • 13Thoracic Surgery, Kinki University Faculty of Medicine, 589-8511 - Osaka-Ssayama/JP
  • 14G. Papanikolaou Hospital, Pulmonary Department, Aristotle University of Thessaloniki, 57010 - Thessaloniki/GR
  • 15Chemotherapy, Regional Oncology Center, 454004 - Chelyabinsk/RU
  • 16Medical Governance And Bioethics, GSK vaccines, 1330 - Rixensart/BE
  • 17Dept. Clinical Oncology, GlaxoSmithKline Biologicals, BE-1330 - Rixensart/BE
  • 18Thoracic Division, Department of Cardiothoracic Surgery, 10065 - New York/US

 

Abstract

Aim

Adjuvant chemotherapy (ACT) is the standard of care for Stage II and IIIA NSCLC, and for high risk Stage IB NSCLC. However, the 5-year disease-free survival remains poor (35-50%) and about half of the patients will not receive ACT for various reasons. This Phase III trial investigated whether the recMAGE-A3 + AS15 cancer immunotherapeutic (MAGE-A3 CI) as adjuvant therapy improved disease-free survival (DFS) in patients with resected NSCLC.

Methods

MAGRIT was a randomized, double-blind, placebo-controlled trial in patients with completely resected MAGE-A3-positive NSCLC Stages IB, II, and IIIA (TNM version 6) and who did or did not receive ACT. Patients were randomly assigned (2:1) to receive 13 intramuscular injections of MAGE-A3 CI or placebo over a 27-month (m) treatment period. The three co-primary endpoints were DFS in the overall and in the no-ACT population and DFS in patients with a potentially predictive gene signature (GS).

Results

Out of 13,849 patients screened, 4,210 patients had a MAGE-A3 positive tumour sample and 2,272 patients were randomised and treated. Overall, 52% of the patients received ACT; 47%, 36% and 17% were Stage IB, II and IIIA, respectively. Median age was 63 years and 24% of patients were females. Mean relative dose intensity was above 98% in both groups throughout the treatment period. Median follow-up at the time of final analysis was 38.8m. Median DFS was 60.5m and 57.9m respectively for MAGE-A3 CI and placebo (HR 1.024, 95% CI 0.891-1.177; p = 0.7379). In patients who did not receive ACT, median DFS was 58.0m and 56.9m for MAGE-A3 CI and placebo groups, respectively (HR 0.970, 95% CI 0.797-1.179; p = 0.7572). The rate of grade ≥ 3 adverse events (16%) did not differ between treatment groups.

Conclusions

Treatment of NSCLC patients with MAGE-A3 CI did not increase DFS compared to placebo in either the overall population or in patients who did not receive ACT. Due to the absence of treatment effect, a GS predictive of clinical benefit to MAGE-A3 CI could not be identified. Funding Source: GlaxoSmithKline Biologicals SA.

Disclosure

J.F. Vansteenkiste: Pr Vansteenkiste received GSK fees as Primary investigator for the MAGRIT study; B. Cho: Dr Cho received consultancy fees from Novartis and Boehringer-ingelheim; T. De Pas: No conflicts of interest. Fee received from GSK as member of steering committee of the study; J. Jassem: Dr Jassem received grant and personal fees for Consultancy from GSK; M. Yoshimura: Pr Yoshimura received GSK fees as Primary investigator for the MAGRIT and PEARL study; H. Nakayama: Dr Nakayama received GSK fees as Primary investigator for the MAGRIT and PEARL study; T. Mitsudomi: Dr Mitsudomi received personal fees from GSK for an advisory role; B. Spiessens: Bart Spiessens is employee of GSK and do own stock options of GSK; V. Brichard: Dr Birchart is GSK employee and do own Stock options from GSK; C. Debruyne: Dr Debruyne is GSK employee and do own GSK stock options; P. Therasse: GSK employee and Stock options owner; N. Altorki: Dr Altorki received GSK fees for trial conduct of GSK studies. All other authors have declared no conflicts of interest.