Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial

Background Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC. Methods 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818. Findings 6-month PFS was 43.2% (32 of 74; 95% CI 33.4-53.5) in the TG4010 plus chemotherapy group, and 35.1% (26 of 74; 25.9-45.3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23.3%) versus six of 72 (8.3%), 12 (16.4%) versus two (2.8%), and four (5.5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45.2%] of patients in the TG4010 plus chemotherapy group vs 31 [43.1%] in the chemotherapy alone group) and fatigue (18 [24.7%] vs 13 [18.1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4.1%] vs 10 [13.9%]) and pleural effusion (none vs four [5.6%]). 38 of 73 patients (52.1%) in the TG4010 plus chemotherapy group and 34 of 72 (47.2%) in the chemotherapy alone group had at least one serious adverse event. Interpretation This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated.