4081 Background: BTCs are a group of relatively rare malignancies comprised of intrahepatic cholangiocarcinoma (CCA), extrahepatic CCA, and gallbladder cancer. The first-line standard of care of gemcitabine and cisplatin (GC) has remained unchanged for the past decade, highlighting the need for novel therapies. The TOPAZ-1 trial demonstrated improved progression-free (PFS) and overall survival (OS) with durvalumab added to GC. This trial-based economic evaluation estimated the cost-effectiveness/utility of DGC versus GC from a US payer perspective. Methods: A three state partitioned survival model (Progression-free, Progressed, Death) was developed to compare costs and overall survival outcomes associated with both treatments. PFS and OS curves were digitized, and parametric functions fitted. A 5-year time horizon with a 3% discount rate/year was considered. Costs of treatment (average sales price), administration, and monitoring parameters were sourced from Centers for Medicare & Medicaid Services databases; costs of adverse event management (grade 3/4 with rate ≥ 5%) were sourced from prior BTC economic evaluations. Life years (LY), quality adjusted life years (QALY), incremental cost-effectiveness and utility ratios (ICER/ICUR) were estimated in a base case (BCA) and probabilistic sensitivity analyses (PSA). A cost-effectiveness acceptability curve (CEAC) was plotted to determine the probability of either treatment being cost-effective over the other at different willingness to pay (WTP) thresholds. Results: Exponential regression was used to extrapolate DGC and GC survival curves. As shown in the table, the BCA (PSA) shows an incremental cost of DGC over GC of 131,350 (131,212), incremental LY of 0.38 (0.38), and incremental QALY of 0.26 (0.28). The BCA and (PSA) ICERs reveal an additional 345,658 (345,295) per LY gained (g) and an additional 505,192 (468,614) per QALYg. The CEAC curve shows that DGC treatment has a 50% probability of being cost-effective at a WTP threshold value of 525,000 and 100% probability at a threshold of 1,375,000 or above. Conclusions: This economic evaluation demonstrates that, in the setting of advanced BTC, DGC is associated with a slight improvement in LY and QALY, yet at a marked incremental cost, requiring a very high WTP threshold. [Table: see text]