Background: CNS mets occur in 20%–40% of pts with adv NSCLC and are associated with poor overall survival (OS; median ≈7 mo). We evaluated nivo in this subgroup by: 1) pooling nivo-treated pts with adv NSCLC and pretreated (pretx) stable CNS mets at baseline (BL) across CheckMate 063 (phase [ph] II), 017 (ph III), and 057 (ph III); and 2) comparing OS with nivo vs docetaxel (doc) in pts with stable BL CNS mets in CheckMate 017 and 057. Methods: 1) Nivo-treated pts with adv NSCLC and pretx BL CNS mets from CheckMate 063 (n = 3), 017 (n = 9), and 057 (n = 34) were pooled to assess BL characteristics, safety, and CNS progression. 2) OS was analyzed in pts with pretx BL CNS mets and squamous (SQ; CheckMate 017) or non-SQ (NSQ; CheckMate 057) NSCLC treated with nivo 3 mg/kg Q2W vs doc 75 mg/m² Q3W. Results: Of 46 nivo-assigned pts with pretx CNS mets, 74% had prior CNS-site radiotherapy and 85% had ≥ 2 extra-CNS sites of mets. Median follow-up was 8.4 mo (range: 0.3, 23.4); median treatment duration (n = 45; 1 pt not treated) was 2.3 mo (range: 0.03, 23.3). Any grade (gr) treatment-related (TR) adverse events (AEs) occurred in 67% of pts; gr 3–4 TRAEs occurred in 7%, with no TR deaths. CNS TRAEs occurred in 5 pts (11%) and were all gr 1–2 (paresthesia, n = 2; dizziness, somnolence, and tremor, n = 1 each). At time of overall disease progression (PD) or last tumor assessment, 33% of pts had no evidence of CNS progression (stable/decreased CNS lesions) and 52% had unequivocal progression in the CNS (15% had no post-BL CNS assessment). In pts with pretx CNS mets from CheckMate 017, median OS (events, n; HR) with nivo (n = 9) vs doc (n = 8) was 4.99 mo vs 3.86 mo (6 vs 8; not determined); in CheckMate 057, median OS with nivo (n = 34) vs doc (n = 34) was 7.61 mo vs 7.33 mo (30 vs 27; 1.04, 95% CI: 0.62, 1.76). Conclusions: Nivo was well-tolerated in pts with adv NSCLC and pretx CNS mets, with generally low-grade toxicities. One-third of pts had no evidence of CNS progression at time of PD/last assessment. In pts with SQ and NSQ NSCLC with pretx CNS mets, median OS was similar with nivo vs doc. Additional results (including OS and CNS progression rates in pts with/without pretx CNS mets and safety/efficacy of nivo in pts with untreated BL CNS mets from CheckMate 012) will be presented. Clinical trial information: NCT01721759; NCT01642004; NCT01673867