A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).

Trial ID #	NCT03737643; DUO-O
Phase	III
Drug Class	DNA Damage Repair Pathway Inhibitors: PARP
Drug Name	Olaparib
Alternate Drug Names	AZD2281, Lynparza
Drugs in Trial	Bevacizumab, Carboplatin, Durvalumab, Olaparib, Paclitaxel
Eligible Participant	Newly diagnosed stage III/IV high grade non-gBRCA MUT ovarian cancer (neo-adjuvant or adjuvant and maintenance)
Patients Enrolled	1130
Therapy Setting	First-line
Study Design	Double Blind, Randomized
Endpoints	PFS, OS, evaluated per RECIST
Biomarkers	tBRCA status, Exploratory: HRD status
Efficacy	CarboPt+Pac+Bev+Dur w/Bev+Dur+Ola maint vs CarboPt+Pac+Bev+Dur w/ Bev+Dur+Ola Placebo maint (n= 374) vs CarboPt+Pac+Bev+Dur Placebo w/ Bev+Dur placebo (n=378) +Ola Placebo maint: ITT (excl. BRCA MUT): PFS: 25.1 vs 20.6 vs 19.3 months; HR: 0.61 (0.51-0.73, p<0.0001); HR: 0.87 (0.74-1.03, p=0.11) 24 months PFS: 53.0 vs 38.7 vs 33.2% OS: 48.5 vs NR vs 48.0 months; HR: 0.95 (0.76-1.20, p=0.68); HR: 0.92 (0.73-1.16) 24 months OS: 83.3 vs 81.2 vs 79.8% HRD+ (excl. BRCA MUT): PFS: 45.1 vs 25.1 vs 23.3 months; HR: 0.46 (0.33-0.65, p<0.0001); HR: 0.89 (0.67-1.19) 24 months PFS: 72.9 vs 50.9 vs 46.5% OS: NR vs NR vs NR; HR: 0.84 (0.51-1.37); HR: 0.69 (0.41-1.15) 24 months OS: 96.4 vs 91.7 vs 88.6% Exploratory analysis; HRD-: PFS: 21.1 vs 15.4 vs 17.5 months; HR: 0.68 (0.54-0.85); HR: 0.92 (0.74-1.14) 24 months PFS: 41.1 vs 30.9 vs 26.1% OS: 41.1 vs 30.9 vs 26.1 months; HR: 0.99 (0.76-1.31); HR: 1.05 (0.80-1.38) 24 months OS: 76.4 vs 73.0 vs 76.9%
Clinically Significant Adverse Events	CarboPt+Pac+Bev+Dur w/Bev+Dur+Ola maint vs CarboPt+Pac+Bev+Dur w/ Bev+Dur+Ola Placebo maint (n= 374) vs CarboPt+Pac+Bev+Dur Placebo w/ Bev+Dur placebo (n=378) +Ola Placebo maint: Serious AE: overall (39 vs 43 vs 34%); MDS/AML: (2 vs 0 vs 1) Grade 3-4 AE: overall (71 vs 66 vs 61%); neutropenia (31 vs 28 vs 26%); anemia (24 vs 8 vs 8%)
Conclusion	CarboPt+Pac+Bev+Dur followed by maintenance Bev+Dur+Ola in patients with newly diagnosed non-tBRCAm advanced OC resulted in a statistically significant and clinically meaningful improvement in PFS vs CarboPt+Pac+Bev followed by maintenance Bev. Safety was generally consistent with the known profiles of each agent
Reference	Harter P et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): Results from the randomized, placebo (pbo)-controlled phase III DUO-O trial. J Clin Oncol 41, 2023 (suppl 17; abstr LBA5506) https://ascopubs.org/doi/10.1200/JCO.2023.41.17_suppl.LBA5506 Harter P et al. Slide from presentation https://www.clearityfoundation.org/wp-content/uploads/2023/08/DUO-O-slide-ASCO-2023.pdf Harter P et al. Durvalumab plus paclitaxel/carboplatin plus bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance among patients with newly-diagnosed advanced ovarian cancer without a tumor BRCA1/BRCA2 mutation: Updated results from DUO-O/ENGOT-OV46/GOG-3025 Trial. SGO (2024) https://www.clearityfoundation.org/wp-content/uploads/2024/05/Harter-et-al.-DUO-O-SGO-2024.pdf

A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (DUO-O).

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