398 Background: Prior prognostic models for 2nd-line systemic therapy have not been studied in the setting of contemporary sequential targeted therapy (TT). We sought to validate the IMDC prognostic model in patients with mRCC receiving next-line TT after progression on 1st-line TT. Methods: Patients who received 2nd-line TT after progressing on 1st-line TT for mRCC at 19 centres were analyzed. For the patients who had immunotherapy (22%) prior to their 1st TT, we examined their second TT (ie 3rd-line therapy). The endpoint was median overall survival (OS) since the initiation of 2nd-line therapy. Additionally, we compared the IMDC model with the 3-factor-MSKCC model (Motzer et al JCO 2004) used for previously-treated patients. Results: 1,021 patients treated with a second TT were included. Median time on 2nd-line TT was 3.9 months (range 0-76+). 871 (85%) of patients had stopped 2nd-line TT by the time of analysis. Median OS since 2nd-line TT was 12.5 months (95% CI: 11.3-14.3 months), with 369 (36.1%) of patients remaining alive. 5 out of 6 pre-defined factors in IMDC model (anemia, thrombocytosis, neutrophilia, KPS <80%, and <1 year from diagnosis to treatment) measured at the time of 2nd-line TT were independent predictors of poorer OS (HR between 1.39 and 1.58, p<0.05). Hypercalcemia was not statistically significant in multivariable analysis (p=0.3008) likely due to the low incidence of hypercalcemia (9%). The concordance index using all 6 prognostic factors was 0.70, and was 0.66 with the 3-factor-MSKCC model. When patients were divided into 3 risk categories using IMDC criteria, median OS was 35.8 months (95% CI 28.3-47.8) in the favorable risk group (n=76), 16.6 months (95% CI 14.9-17.9) in the intermediate risk group (n=529), and 5.4 months (95% CI 4.7-6.8) in the poor risk group (n=261). Conclusions: The IMDC prognostic model has been validated in and can be applied to patients previously treated with TT, in addition to previously validated populations in 1st-line TT and non-clear cell setting.