Background: Nivo is the only immunotherapy to significantly improve overall survival (OS) in pts with platinum (plt)–refractory R/M SCCHN. In the randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), nivo significantly improved OS vs IC (HR [95% CI] = 0.68 [0.54, 0.86]) in pts with R/M SCCHN who had progressed on or within 6 mo of plt-based therapy. The safety profile of nivo in the overall pt population was favorable compared with IC. With conventional treatments, there has been concern regarding efficacy and tolerability in elderly patients owing to age-related factors and comorbidities. Here we describe efficacy and safety of nivo compared with IC, by age. Methods: Eligible pts were randomized 2:1 to nivo 3 mg/kg every 2 weeks (n = 240) or IC (methotrexate, docetaxel, or cetuximab, n = 121). The primary endpoint was OS. Outcomes were analyzed by age < 65 and ≥65 yrs. Data cut: September 2017 (minimum follow-up: 24.2 mo). Results: At baseline, 68 pts (28.3%) in the nivo arm and 45 pts (37.2%) in the IC arm were ≥65 yrs old. Baseline characteristics and relative nivo dose intensity were generally similar across age groups. OS and tumor response benefits with nivo vs IC were maintained regardless of age (Table). The 30-mo OS rates of 11.2% ( < 65 yrs) and 13.0% (≥65 yrs) with nivo were more than tripled vs corresponding IC rates of 1.4% and 3.3%, respectively. As in the overall pt population, the nivo arm had a lower rate of treatment-related adverse events (TRAEs) vs IC (Table). Conclusions: Nivo improved OS and objective response rate (ORR) vs IC in pts < 65 yrs and ≥65 yrs in CheckMate 141, with a manageable safety profile in both age groups. OS benefit with nivo was maintained through 2 yrs of follow-up for both groups. These data support the use of nivo, regardless of age, in pts with R/M SCCHN who progress within 6 mo of plt therapy. Clinical trial information: NCT02105636