Background: Cisplatin-based chemotherapy and concurrent radiotherapy, the standard treatments for locally advanced unresectable NSCLC have reach a plateau. New therapeutic combinations of molecular targeted drugs are needed. IFCT-0803 phase II trial aimed to evaluate the benefit of adding cetuximab to a combination of radio and concomitant chemotherapy with cisplatin and pemetrexed in patients with stage III, non-squamous NSCLC. Methods: Based on a 2-stage Simon approach, a total of 106 patients were to accrue. An interim analysis of the first 34 patients authorized the continuation of the study. Eligible patients receive thoracic radiation (66 Gy) along with cisplatin (75 mg/m²) and pemetrexed (500 mg/m²) on D1 administered every 21 days for four cycles; weekly cetuximab (400 mg/m²) for the first week, then 250 mg/m²) is added from the first week of therapy for a total of 12 doses. The primary objective is to assess the disease control rate at the 16th week (16W-DCR), one month after the treatment completion. Results: 99 patients at inclusion were: 60 male, 57 years (median age), PS 0 = 60, ever smoker = 7, stage IIIA = 48 and IIIB = 49, adenocarcinoma = 77. Compliance was good for the first 92 eligible patients : Day 1 chemotherapy was administered to 100% of patients on cycle 1, 98.9% on cycle 2, 93.4% on cycle 3 and 84.8% on cycle 4. Radiotherapy protocol was respected: median was 33 for number of fractions, 66 Gy for total dose, 48 days for treatment duration. The endpoint 16W-DCR was 93.3 % (IC95% : 88.1 - 98.5). 30 patients had a maximal toxicity of grade 3 and 10 of grade 4. Two toxic deaths were observed, one by a traumatic subdural hematoma, as the patient experienced a grade 4 thrombocytemia, another occuring two months post-treatment completion, caused by a grade 4 radiation pneumonia, whereas concurrent cancer progression was documented. Conclusions: IFCT-0803 trial showed both the feasability and high DCR for radiation, cisplatin, pemetrexed and cetuximab combination, with a tolerable toxicity profile. Our data will be updated at the ASCO meeting, the accrual goal (106 pts) being reached on Jan. 2014. Clinical trial information: NCT01102231.