BACKGROUND Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of > 5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500 mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression‐free survival, overall survival, and toxicity. RESULTS All 26 patients were men with a median age of 68 years (range, 52‐80 years). The majority of patients were ever‐smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7‐8.6 months). The overall response rate was 11.5% (95% confidence interval 95% CI, 0.8%‐23.8%) and the disease control rate was 50% (95% CI, 30.8%‐69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months, ≥ 5.1 months, and 6.1 months, respectively. After a median follow‐up of 15.7 months (range, 1.2‐25.6 months), the median overall survival was 5.0 months (95% CI, 3.6‐6.4 months) and the median progression‐free survival was 2.9 months (95% CI, 1.5‐4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0). CONCLUSIONS Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted. Cancer 2016;122:3024‐3031. © 2016 American Cancer Society. Dovitinib demonstrates an objective response rate of 11.5% (95% confidence interval, 0.8%‐23.8%) in patients with advanced squamous cell cancer of the lung whose tumors demonstrate fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization assay. Further research to evaluate predictive biomarkers correlated with the efficacy of fibroblast growth factor receptor inhibitors is needed. See also pages 2938‐40.