Background: In previous analyses of the phase 3, double-blind KEYNOTE-716 study, adjuvant pembrolizumab (pembro) significantly improved recurrence-free survival compared with placebo in patients (pts) with resected AJCC-8 stage IIB or IIC melanoma. We present new data from the analysis of distant metastasis-free survival (DMFS), and recurrence-free survival (RFS) with longer follow up. Methods: A total of 976 pts aged ≥12 years with complete resection of cutaneous stage IIB or IIC melanoma and negative sentinel lymph node biopsy were randomized 1:1 to pembro 200 mg (2 mg/kg for pediatric pts) or placebo Q3W for 17 cycles (approximately 1 year) in Part 1 of the study. Randomization was stratified by T category 3b, 4a, 4b (adults) with a separate stratum for pediatric pts. Treatment continued until disease recurrence or unacceptable toxicity. Pts who received placebo in Part 1, or who did not experience disease progression within 6 months of completing Part 1 were eligible for additional cycles of pembro Q3W at recurrence (Part 2). The primary endpoint was RFS per investigator. DMFS by investigator is a secondary endpoint. The data cut-off date for this interim analysis was Jan 4th, 2022. Results: At median follow-up of 26.9 mo (range, 4.6-39.2), adjuvant pembro significantly improved DMFS (HR 0.64, 95% CI, 0.47-0.88; P=0.0029; median not reached [NR] for both) vs placebo. The 24-mo DMFS rate was 88.1% vs 82.2%. There was consistent reduction in the risk of recurrence with pembro vs placebo (HR 0.64, 95% CI, 0.50-0.84) with further follow-up. The 24-mo RFS rate was 81.2% vs 72.8%. Grade ≥ 3 any-cause AEs occurred in 137 (28.4%) vs 97 (20.0%) pts in the pembro vs placebo arms. Grade ≥ 3 drug-related AEs occurred in 83 (17.2%) vs 24 (4.9%) pts. One pt in the pembro arm and 5 pts in the placebo arm died due to an any-cause AE. No deaths were drug-related. Immune-mediated AEs occurred in 182 (37.7%) vs 45 (9.3%) pts, most commonly hypothyroidism (17.2% vs 3.7%). Conclusions: Adjuvant pembrolizumab vs placebo for resected stage IIB and IIC melanoma significantly improved DMFS, with continued reduction in the risk of recurrence, and a favorable benefit-risk profile. Clinical trial information: NCT03553836.