Background: CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods: Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m² D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results: Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed the first 57 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 50/50%; smokers 45.5%; adenocarcinoma/squamous 34.8/43.9%; stage IIIA/B 43.9/56.1%. Only 29.8% of pts presented any grade 3-4 adverse event, including: neutropenia 22.8%; anemia 3.5%; febrile neutropenia 7%; esophagitis 1.8%; pneumonitis 1.8%. There were two deaths non-related to the treatment, during this period. Forty-four pts have completed the treatment. ORR: 66.7%. DCR: 79%. With a median follow-up of 11.2 months (range 1.1-21.7), the median PFS is 11.9 months (CI95%; 10.1-NR). Conclusions: mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. EudraCT 2015-003312-21. Clinical trial information: EudraCT 2015-003312-21.