Background: The first interim analysis of KEYNOTE-826 (NCT03635567) showed that first-line pembrolizumab (pembro) + chemotherapy (chemo) provided statistically significant and clinically meaningful improvements in OS and PFS vs placebo (pbo) + chemo in patients (pts) with recurrent, persistent, or metastatic cervical cancer across all prespecified populations (PD-L1 combined positive score [CPS] ≥1, all-comer, and CPS ≥10). Here, we present the protocol-specified final OS analysis results of KEYNOTE-826. Methods: Eligible adults with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemo (prior radiosensitizing chemo allowed) and not amenable to curative treatment (surgery or radiation) were randomized 1:1 to pembro 200 mg or placebo Q3W for up to 35 cycles + chemo (paclitaxel 175 mg/m² + cisplatin 50 mg/m² or carboplatin AUC 5), ± bev 15 mg/kg. Pts were stratified by metastatic status at diagnosis (yes/no), planned bev use (yes/no), and PD-L1 CPS (<1, 1 to <10, or ≥10). Dual primary end points were OS and PFS per RECIST v1.1 assessed by investigator review, each tested sequentially in the PD-L1 CPS ≥1, all-comer, and CPS ≥10 populations. Results: From Nov 2018 to Jan 2020, 617 patients were randomized (pembro + chemo, n = 308 [63.6% with bev]; pbo + chemo, n = 309 [62.5% with bev]); 548 (88.8%) pts had PD-L1 CPS ≥1 and 317 (51.4%) had CPS ≥10. At the Oct 3, 2022 data cutoff, median follow-up was 39.1 mo. Pembro + chemo significantly improved OS and PFS in the CPS ≥1, all-comer, and CPS ≥10 populations (Table). The pembro + chemo benefit was seen regardless of bev use. Grade ≥3 AE incidence was 82.4% in the pembro + chemo arm and 75.4% in the placebo + chemo arm. The most common grade ≥3 AEs were anemia (30.3% vs 27.8%), neutropenia (12.4% vs 9.7%), and hypertension (10.4% vs 11.7%). Conclusions: The addition of pembro to chemo ± bev significantly reduced the risk of death by 40% in the PD-L1 CPS ≥1 population, by 37% in the all-comer population, and by 42% in the CPS ≥10 population, and had a manageable safety profile. These data are consistent with the earlier results and provide further support for pembro + chemo ± bev as a new standard of care for first-line treatment of persistent, recurrent, or metastatic cervical cancer. Clinical trial information: NCT03635567.