Background: Immunotherapy response patterns differ from traditional therapies, and pts may benefit from treatment after initial RECIST progression (CCR 2009;15:7412–20). We investigated pts treated beyond progression (TBP) with nivo in study CheckMate 025—nivo vs everolimus (eve) in previously treated pts with aRCC (NCT01668784). Methods: Treatment beyond progression was allowed in pts who had investigator-assessed clinical benefit and tolerated study drug. Pts TBP continued to receive nivo ≥4 wk after first RECIST version 1.1–defined progression to account for any delayed scan results; pts not TBP (NTBP) discontinued treatment after first progression. Pts without progression were excluded from this analysis. Results: Of 406 nivo pts treated, 38% were TBP; 36% were NTBP (of 397 eve pts treated, 17% were TBP; 36% were NTBP—current analysis for nivo only). Baseline characteristics were generally similar except for higher Karnofsky performance status (KPS) ≥90 with TBP vs NTBP (72% vs 62%) and less bulky tumor burden (18% vs 26%). Median overall duration of treatment (DOT) was 8.8 (TBP) and 2.3 mo (NTBP). From randomization to progression, objective response rate was 20% and 14%; median time to response was 1.9 and 3.7 mo; duration of response was 5.6 and 7.0 mo for TBP and NTBP pts, respectively. Treatment-related adverse events occurred in 71% of pts TBP and 70% of pts NTBP before first progression. Characteristics at first progression are shown (Table). Median DOT after first progression was 3.4 mo. Of 140 pts TBP with tumor measurements before and after progression, 14% had ≥30% tumor burden reduction from first progression. Median overall survival was 28.1 (TBP) vs 15.0 mo (NTBP); P<0.001.Conclusions: Treatment beyond progression with nivo can be associated with tumor shrinkage after progression. Evaluating disease characteristics at first progression may facilitate decision making to continue nivo treatment beyond progression. Clinical trial information: NCT01668784