9554 Background: Pembro monotherapy is approved in certain countries, including the US, for treatment of LA or R/M cSCC based on results from the open-label phase 2 KEYNOTE-629 trial (NCT03284424). Promising antitumor activity was demonstrated with pembro in both the LA and R/M cohorts. ORR (95% CI) was 50.0% (36.1-63.9; 16.7% CRs) in the LA cohort and 35.2% (26.2-45.2; 10.5% CRs) in the R/M cohort. We present data from KEYNOTE-629 with an additional follow-up of 38 mo for LA and R/M cohorts. Methods: Adults with histologically confirmed LA or R/M cSCC, measurable disease per RECIST v1.1 by blinded independent central review (BICR), and ECOG PS 0 or 1 received pembro 200 mg IV every 3 weeks for up to 35 cycles (~2 years). The primary end point was ORR per RECIST v1.1 by BICR. Secondary end points were DOR, DCR (CR + PR + SD ≥12 wks), and PFS per RECIST v1.1 by BICR; OS; and safety. End points were analyzed in pts who received ≥1 dose of pembro. Results: A total of 159 pts were treated with pembro (LA, n = 54; R/M, n = 105). As of September 13, 2023, 33 pts (20.8%) completed treatment and 126 pts (79.2%) discontinued treatment. Median (range) follow-up was 52.4 mo (47.6-56.9) for the LA cohort, 64.7 mo (62.1-69.5) for the R/M cohort, and 63.1 mo (47.6-69.5) in the total population. ORR and DCR are shown in the table. Median DOR (range) was 47.2 mo (1.0+ to 49.9+) in the LA cohort, not reached (NR; 2.7 to 64.2+ mo) in the R/M cohort, and 52.5 mo (1.0+ to 64.2+) in the total population; the proportion of responders with responses ≥12 mo by Kaplan-Meier estimate were 84.8%, 77.8%, and 80.7%, respectively. Median (95% CI) PFS was 14.4 mo (5.5-43.6) in the LA cohort, 5.7 mo (3.1-8.5) in the R/M cohort, and 8.0 mo (5.3-14.4) in the total population; 12-mo rates were 56.7%, 37.3%, and 43.7%, respectively. Median (95% CI) OS was NR (33.3-NR) in the LA cohort, 23.8 mo (13.4-30.9) in the R/M cohort, and 29.8 mo (20.0-42.8) in the total population; 36-mo rates were 62.0%, 39.5%, and 47.0%, respectively. Grade 3-5 treatment-related AEs occurred in 11.3% of pts, and grade 3-5 immune-mediated AEs and infusion reactions occurred in 8.8% of pts. Two pts (1.3%) died due to a treatment-related AE (colitis, cranial nerve disorder). Conclusions: With a median follow-up of more than 5 years, pembro continued to show durable responses in pts with LA or R/M cSCC. No new safety signals were observed. Results from this study continue to support the use of pembro in this pt population. Clinical trial information: NCT03284424 . [Table: see text]