Trial Proactive: A Prospective, Randomized, Multicenter, Open Label Phase Iii Study Of Active Specific Immunotherapy With Racotumomab Plus Best Support Treatment Versus Best Support Treatment In Patients With Advanced Non-Small Cell Lung Cancer

TPS3123 Background: Gangliosides, especially NeuGc-GM3, are attractive targets for cancer immunotherapy. They are not expressed in normal human cells but are overexpressed and involved in tumor growth in several tumors (melanoma, neuroectodermal pediatric tumors and breast cancer). More than 70% of non-small cell lung cancers (NSCLC) express NeuGc-GM3. Racotumomab is an anti-idiotypic monoclonal antibody that mimics NeuGc gangliosides. Administered as a therapeutic vaccine it acts as an antigen, inducing a cellular and humoral immune response against NeuGc-GM3 and other gangliosides. Previous trials have shown its low toxicity and high immunogenicity. Recently, a multicenter, randomized, placebo controlled, double-blind trial in 176 NSCLC (IIIB and IV) patients with at least stable disease after first line therapy and progression free at inclusion showed a statistical significant survival benefit in favor of racotumomab. Methods: This phase III, multinational, randomized (1:1), open label trial will evaluate efficacy and safety of racotumomab plus best supportive care (BSC) versus BSC. 1,082 patients with NSCLC (stages III or IV) showing response or stable disease after standard first-line therapy (platinum-based chemotherapy and radiotherapy) are eligible if they remain free of progression and have a PS ≤ 1. Vaccination consists of an induction period (5 doses, 1 every 14 days) followed by a maintenance period (1 dose every 28 days, until worsening of the PS or unacceptable toxicity occur). Upon progression other onco-specific therapies may be used and vaccination can continue. Overall survival (OS) will be compared using a two-sided log rank test at a significance level (alpha) of 0.05 with 90% power to detect a hazard ratio of 0.79. There will be 3 interim analyses and a final analysis when 758 deaths occur. So far 190 patients have been randomized. An Independent Data Monitoring Committee oversees the study and has so far (last meeting September 2012) concluded that the trial can continue. The trial is registered in ClinicalTrials.gov under NCT01460472. Clinical trial information: NCT01460472.