Impact of claudin-1 (CLDN1) expression on molecular correlates and clinical outcomes in patients with advanced biliary tract cancers (BTCs).

602 Background: The tight junction protein CLDN1 is a potential therapeutic target in many cancers where its dysregulation is associated with invasiveness and migration. The effect of CLDN1 expression on outcomes in BTC is unknown. We examined the molecular and clinical correlates of CLDN1 expression in a real-world cohort of patients (pts) with advanced BTCs, including across subtypes. Methods: We used Tempus Lens, a platform used to query multimodal data from millions of de-identified patient records in the Tempus Database to identify 1,897 pts with BTCs whose tumors were tested with Tempus xT and xR panels. RNA-seq data were normalized by computing transcripts per million (TPM) and transforming them by log2(TPM+1). PD-L1 status was assessed with the 22C3 clone and immune cell infiltration was estimated using quanTIseq. Pts were classified into CLDN1-high (CLDN1-H) vs CLDN1-low (CLDN1-L) by median CLDN1 expression. P-values were calculated by either χ2 or Fisher’s exact tests. Real-world overall survival (rwOS) was defined as the time from the initiation of first-line (1L) treatment with chemotherapy(chemo) +/- immunotherapy (IO) (N=919) to the earliest of death, last known follow up, or max 5 years. Median rwOS (mOS) was estimated with Kaplan-Meier curves and log-rank p-value. Statistical significance was set at p≤0.05; all tests were two-sided. Results: The 1,897 patient cohort was comprised of 51% IHCC, 14% EHCC, 22% GB, 13% CCA NOS. Median age 65 yrs; 53% female. IHCC tumors had more frequent CLDN1-H expression (70%), while EHCC (81%) and GB (78%) tumors had more frequent CLDN1-L expression (p