TG4010 immunotherapy plus chemotherapy as first-line treatment of advanced non small cell lung cancer (NSCLC): Phase IIb results of the TIME trial

Abstract

Background: TG4010 is an immunotherapy using an attenuated and modified poxvirus (MVA) coding for MUC1 and interleukin-2 to induce a cellular immune response against MUC1 expressing tumors. Previous Phase 2 trials have demonstrated the efficacy and safety of TG4010 in combination with chemotherapy. In addition, level of Triple Positive Activated Lymphocytes (TrPAL; CD16+, CD56+, CD69+) was identified as a potential biomarker predictive of efficacy. Methods: TIME is a double blind, placebo-controlled Phase IIb/III study. The Phase IIb part compared first-line chemotherapy combined with TG4010 or placebo and further assessed the predictive value of baseline level of TrPAL. Eligibility criteria included previously untreated stage IV NSCLC, MUC1+ tumor by immunohistochemistry, PS 95% that the PFS HR is < 1 in pts treated with TG4010. Preplanned subgroup analyses were performed using an optimal cut-off value for the level of TrPAL defining 2 subpopulations (low and high TrPAL). In 147 patients with low TrPAL, PFS was significantly increased in TG4010 arm (HR=0.66 [CI95% 0.46-0.94] p= 0.010) as well as OS (HR=0.67 [CI95%0.46-0.98) p=0.018) while there was no benefit in pts with high TrPAL. Activity was even more important in patients with low TrPAL and non-squamous tumor (n=127) with PFS HR =0.59 (CI95% 0.40-0.87; p=0.003), and OS HR=0.59 (CI95% 0.39-0.91; p=0.007). In this subgroup, ORR was 39.3% vs 30.3% and duration of response 43.1 vs 18.1weeks in TG4010 and placebo arms, respectively. TG4010 related adverse events were mainly low-grade injection site reactions. The impact of PDL1 expression by immunohistochemistry in the tumor of patients treated with TG4010 supports the activity of TG4010 whether the tumor is positive or negative for PDL1 expression. Conclusions: These results provide further evidence of the efficacy of TG4010 in combination with chemotherapy in NSCLC and of the potential of TrPAL as a predictive biomarker. Future development of TG4010 is being planned, both in combination with chemotherapy (Phase 3 part of the TIME trial) and in combination with immune checkpoint inhibitors.