Time, a Phase 2B/3 Study Evaluating Tg4010 in Combination with First Line Therapy in Advanced Non Small Cell Lung Cancer (Nsclc). Phase 2B Results

Aim: TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16 + CD56 + CD69+) might be a predictive biomarker for TG4010 efficacy in NSCLC (Lancet Oncol 2011;12:1125-33). TIME is a double-blind phase 2b/3 study (NCT01383148) comparing the combination of first line therapy with TG4010 or placebo. The Phase 2b part aims at prospectively validating the baseline TrPAL level as a predictive biomarker. Methods: Primary endpoint of the Phase 2b part of the study was to compare progression-free survival (PFS, according to RECIST 1.1) between TG4010 and placebo arms using a Bayesian design, in stage IV NSCLC patients with a MUC1+ tumor. Secondary objectives were response rate, safety, survival and subgroup analyses. A dynamic minimization procedure was applied at randomization for histology, prescription of bevacizumab, type of chemotherapy, performance status and center. Results: 217 patients have been enrolled out of which 170 patients with a normal TrPAL level (pre-determined threshold) and an analysis of PFS was conducted in this cohort after 137 events of progression were recorded. The hazard ratio (HR) for PFS is 0.76 (95%CI: 0.54-1.06). This corresponds to a 97.5% Bayesian probability that the true HR is Conclusions: These data support the predictive value of the TrPAL biomarker. They also confirm TG4010 efficacy and safety profile in stage IV NSCLC patients and warrant the continuation of the TIME study with its Phase 3 part. Disclosure: E. Quoix: Transgene: joint steering committee member and consultant; C. Chouaid: Consultant for Lilly, GSK, Amgen Advisory board member: Lilly, Roche, AZ, Amgen, Boheringer Ingelheim; Z. Papai: Advisory board member for Transgene; V. Westeel: Advisory board member for Roche, Lilly. Honoraria from Astra Zeneca, Boehringer, Teva; G. Lacoste: Transgene employee. Stockoption ownership; A. Tavernaro: Transgene employee. Stockoption ownership; B. Bastien: Transgene employee. Stockoption ownership; T. Palanche: Transgene employee with Transgene stock options; J. Limacher: Transgene employee. Stock option owner. All other authors have declared no conflicts of interest.