<h3>Introduction/Background</h3> Combination of immunotherapy with carboplatin/paclitaxel (CP) has demonstrated improved progression-free survival (PFS) and overall survival (OS) in patients with advanced endometrial cancer. The Phase III DUO-E/GOG-3041/ENGOT-EN10 trial (NCT04269200) evaluated the addition of durvalumab to standard first-line CP, followed by durvalumab ± olaparib, in patients with endometrial cancer. <h3>Methodology</h3> Patients with newly diagnosed Federation of Gynecology and Obstetrics Stage III/IV or recurrent endometrial cancer and naïve to systemic treatment were randomised 1:1:1 to CP (CP+durvalumab placebo for six cycles followed by durvalumab placebo+olaparib placebo); CP+durvalumab (CP+durvalumab [1120 mg IV q3w] for six cycles followed by durvalumab [1500 mg IV q4w]+olaparib placebo); or CP+durvalumab+olaparib (CP+durvalumab for six cycles followed by durvalumab+olaparib [300 mg tablets bid]). Dual primary endpoints were PFS (investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1) in the intent-to-treat (ITT) population for CP+durvalumab versus CP and CP+durvalumab+olaparib versus CP. OS was a secondary endpoint. A multiple-testing procedure with gatekeeping strategy was applied to PFS and OS. PFS by mismatch repair (MMR) status was a prespecified subgroup analysis. <h3>Results</h3> In the ITT population (N=718), CP+durvalumab and CP+durvalumab+olaparib showed statistically significant and clinically meaningful PFS benefit versus CP (table 1). First interim OS data (27.7% mature) showed a trend towards benefit (CP+durvalumab versus CP: hazard ratio [95% confidence interval] 0.77 [0.56–1.07; P=0.120]; CP+durvalumab+olaparib versus CP: 0.59 [0.42–0.83; P=0.003]). PFS subgroup analysis showed benefit for both arms versus CP in MMR-deficient (dMMR; n=143) and MMR-proficient (pMMR; n=575) patients. In pMMR patients, maintenance olaparib further enhanced PFS benefit (table 1). Safety profiles of the treatment arms were generally consistent with individual components. <h3>Conclusion</h3> DUO-E met both primary endpoints, showing statistically significant and clinically meaningful PFS improvement with the addition of durvalumab to CP followed by durvalumab ± olaparib versus CP alone. Maintenance olaparib further improved PFS in patients with pMMR disease. <h3>Disclosures</h3> This study was funded by AstraZeneca. Previously presented at ESMO 2023, FPN (Final Publication Number): LBA41, S. N. Westin et al – reused with permission.