MAGRIT, a double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of the recMAGE-A3 + AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC)

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.

Plný text abstraktu v časopise Ann Oncol (2014) 25 (suppl 4)