Background: Nintedanib (Vargatef) is an oral triple angiokinase inhibitor targeting VEGF-, PDGF- and FGF receptor pathways. It is approved in the EU and other countries in combination with docetaxel for treatment of locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after 1st line chemotherapy. ICI +/- chemotherapy has changed the standard of care for 1st line treatment of metastatic non-mutated NSCLC. However, currently, only limited clinical data are available to help guide treatment decisions after prior ICI therapy in subsequent lines. Methods: This updated analysis is part of the ongoing NIS VARGADO (cohort B), a prospective non-interventional study of nintedanib + docetaxel after 1st line chemotherapy for adenocarcinoma NSCLC. The analysis includes 57 pts who had previously received both chemotherapy and ICI treatment. Results: Median age was 61 years (range: 45 – 80), 32/57 pts (56.1%) were men, and 41/57 pts (71.9%) were ECOG PS 0/1. 12/57 pts (21.1%) had brain metastases, and 46/57 pts (80.7 %) were current or former smokers. 1st line chemotherapy treatments included pemetrexed (36/57 pts, 63.2%), cisplatin (29/57 pts, 50.9%), carboplatin (33/57 pts, 57.9%), bevacizumab (14/57 pts, 24.6%), vinorelbine (13/57 pts, 22.8%), paclitaxel (8/57 pts, 14.0%), and docetaxel (1/57 pts, 1.8%). 2nd line treatments included nivolumab (34/57 pts, 59.7%), pembrolizumab (14/57 pts, 24.6%), and atezolizumab (7/57 pts, 12.3%). Under nintedanib and docetaxel, ORR was 50% (20/40 pts); DCR was 85.0% (34/40 pts). Median PFS was 6.5 months (95%CI 4.8 – 8.7), median OS was 12.4 months (95%CI 11.4 – 14.1). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation were observed in 30/57 pts (52.6%), 30/57 pts (52.6%), and 17/57 pts (29.8%), respectively. Conclusions: This updated analysis of the VARGADO study continues to show the clinical benefit and manageable safety profile of nintedanib plus docetaxel in patients who had previously received both chemotherapy and ICI treatment. These data add to the real-world evidence that can inform clinical decision-making after prior ICI therapy. Clinical trial information: NCT02392455.