TIME: A phase IIb/III randomized, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC).

Abstract

TPS7610 Background: TG4010 is an immunotherapy product based on a poxvirus (MVA) coding for the MUC1 tumor-associated antigen and interleukin-2. A previous study, TG4010.09, which evaluated the combination of first-line chemotherapy with and without TG4010 in advanced NSCLC, achieved its primary endpoint based on 6-month progression-free survival (PFS) and showed that the pre-treatment level of activated Natural Killer (aNK) cells may be a potential predictive biomarker for TG4010 efficacy (E. Quoix et al., Lancet Oncol. 2011;12:1125-33). Methods: TIME is a double-blind phase IIb/III study comparing the combination of first-line therapy with TG4010 or placebo in stage IV NSCLC patients, Performance Status (PS) 0 or 1 with a MUC1 expressing tumor by immunohistochemistry. The Phase IIb part of the study aims at prospectively validating aNK level as a predictive biomarker with PFS as a primary endpoint, by comparing the two treatment arms in two subgroups defined according to the level of aNK cells at baseline (normal or high). Bayesian criteria, derived from the TG4010.09 study results, will be used to confirm that, with a large probability, the true hazard ratio is <1 in patients with normal level of aNK cells and >1 in patients with high level of aNK cells. The Phase III part of the study will then compare, by using a frequentist approach, the two treatment arms with overall survival as a primary endpoint in the patient population confirmed to be of interest in the Phase IIb part. The phase III part is powered to detect a 27% reduction in the hazard rate of death. Phase IIb and III parts of the study will enroll respectively 206 and 800 patients. A dynamic minimization procedure will be applied at randomization for histology, prescription of bevacizumab, type of chemotherapy, PS and center. If qualifying for, patients will receive maintenance therapy after chemotherapy according to labeling. The study TIME is open to recruitment and referenced in ClinicalTrials.gov with the identifier NCT01383148.