The Lancet Oncology, Early Online Publication, 22 October 2011
Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial
Prof Elisabeth Quoix MD a , Prof Rodryg Ramlau MD b, Prof Virginie Westeel MD c, Zsolt Papai MD d, Anne Madroszyk MD e, Alain Riviere MD f, Piotr Koralewski MD g, Jean-Luc Breton MD h, Erich Stoelben MD i, Denis Braun MD j, Didier Debieuvre MD k, Hervé Lena MD l, Marc Buyse ScD m, Prof Marie-Pierre Chenard MD n, Bruce Acres PhD o, Gisèle Lacoste MD o, Bérangère Bastien MSc o, Annette Tavernaro MSc o, Nadine Bizouarne PhD o, Jean-Yves Bonnefoy PhD o, Jean-Marc Limacher MD o
[Summary]
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 (108 plaque forming units) plus cisplatin (75 mg/m2 on day 1) and gemcitabine (1250 mg/m2 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.
Funding
Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.