Abstract BackgroundWith a 15% of incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and a poor prognostic factor. In BTC, the immune checkpoint inhibitor (ICI) as salvage therapy has modest activity. There was little data on the efficacy of ICIs according to the status of KRAS mutation in BTC. MethodWe conducted molecular profiling in BTC patients who received the ICIs as salvage therapy. Programmed death ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating lymphocytes (TIL) was also assessed. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to the status of PD-L1 expression and KRAS mutation. ResultA total of 62 patients were included in this analysis. The median age was 68.0. 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs. The median lines of prior chemotherapy were 2.5. KRAS mutation was found in 14 patients (22.6%). 28 patients (45.2%) were positive for PD-L1 CPS. There was no statistical correlation between the status of KRAS mutation and PD-L1 expression. The median OS and PFS to ICI were 5.6 (IQR; 3.3 - 8.0) and 3.8 (IQR; 3.0 - 4.5) months, respectively. There were no statistically significant differences in PFS to ICIs according to the status of KRAS mutation (Mutant type vs. Wild type) and PD-L1 expression (Positive vs Negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS as compared to patients with KRAS mutation and PD-L1 negativity (6.5 vs 2.6 months, p=0.047). This finding was not shown in patients with a wild type of KRAS. ConclusionThis analysis showed that PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not the wild type of KRAS. Citation Format: Sun Young Jeong, Jaeyeon Jang, Youngkyung Jeon, Ye Ji Jung, Daeho Choi, Joohyun Hong, Seung Tae Kim, Jung Yong Hong, Joon Oh Park, Young Suk Park, Ho Yeong Lim. The Efficacy of Immune Checkpoint Inhibitors in Advanced Biliary Tract Cancer with KRAS Mutation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4403.