362 Background: N+C demonstrated superior progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 mo median follow-up). N+C maintained efficacy benefits vs S with 44.0 mo median follow-up. Here, we report updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up. Methods: Pts with aRCC were randomized to N 240 mg every 2 weeks + C 40 mg QD vs S 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 y of N. The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Overall, 323 pts were randomized to N+C and 328 to S (ITT). With 55.6 mo median (48.1 mo min.) follow-up for OS, median PFS was 16.4 vs 8.4 mo (hazard ratio [HR] 0.58, 95% CI 0.49-0.70) and median OS was 46.5 vs 36.0 mo (HR 0.77, 95% CI 0.63-0.95) with N+C vs S. ORR (95% CI) was 55.7% (50.1-61.2) vs 27.7% (23.0-32.9); 13.6% vs 4.6% of pts achieved complete response (CR); 6.5% vs 13.7% had progressive disease (PD), respectively. Median (range) time to response (TTR) was 2.8 (1.0-22.2) vs 4.3 (1.7-30.4) mo for N+C vs S, and median (95% CI) duration of response (DOR) was 22.0 (18.0-25.2) vs 15.2 (10.9-19.3) mo. Efficacy by IMDC favorable (FAV) and intermediate/poor (I/P) risk groups is reported in the Table. Among all treated pts (320 pts each arm), any-grade (grade ≥ 3) treatment-related adverse events (TRAEs) occurred in 97.5% (67.5%) vs 93.1% (55.3%) with N+C vs S. Any-grade TRAEs led to discontinuation of N or C in 28.1% of pts (N only, 10.0%; C only, 10.3%; N+C simultaneously, 6.6%; N+C sequentially, 1.3%) and of S in 10.9% of pts. Additional analyses in subgroups of clinical interest will be presented. Conclusions: With 55.6 mo median follow-up, N+C continues to maintain meaningful long-term efficacy benefits over S. No new safety concerns were identified. These results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . [Table: see text]