ARTEMIDE-Biliary02: A phase 3, randomized, global study of rilvegostomig or durvalumab with chemotherapy as first-line (1L) treatment for advanced biliary tract cancer (BTC).

Abstract

TPS4253 Background: Biliary tract cancer (BTC) is the second most common hepatic malignancy, comprising 15% of liver tumors. BTC incidence is rising worldwide, and the majority of patients are diagnosed late where the median survival is approximately one year. Chemoimmunotherapy with gemcitabine and cisplatin combined with either durvalumab or pembrolizumab is the current first-line (1L) standard for advanced BTC. To enhance the clinical benefit from immune checkpoint inhibitors, dual blockade of the programmed cell death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways may be an effective strategy. Rilvegostomig, a monovalent, Fc-reduced, bispecific anti-PD-1/anti-TIGIT antibody, has shown promising preliminary efficacy in combination with gemcitabine and cisplatin for 1L treatment of advanced BTC (Zhou J, et al. ASCO 2025 [Abstract 4080]). The phase 3 ARTEMIDE-Biliary02 study (NCT07221253) assesses the efficacy and safety of rilvegostomig or durvalumab in combination with gemcitabine and cisplatin for 1L treatment of advanced BTC. Methods: Eligible participants (aged ≥ 18 years) have unresectable, locally advanced/metastatic BTC (intrahepatic cholangiocarcinoma [iCCA], extrahepatic CCA [eCCA], or gallbladder cancer [GBC]), previously untreated in the advanced setting, no prior immunotherapy, centrally confirmed programmed cell death ligand-1 (PD-L1) status, and ECOG PS of 0/1. Approximately 1100 participants will be randomized (1:1) to receive rilvegostomig or durvalumab, both in combination with gemcitabine and cisplatin, until radiological progression per RECIST v1.1. Participants will be stratified by PD-L1 expression (tumor area positivity < 1% vs ≥ 1%), disease status (initially unresectable vs recurrent), primary tumor site (iCCA vs eCCA vs GBC), and geographic region (Asia vs rest of world). The primary endpoint is overall survival (OS) in the PD-L1 ≥ 1% population, defined as time from randomization until date of death due to any cause. Key secondary endpoints include OS in the intent-to-treat (ITT) population and progression free survival (PFS), defined as time from randomization until radiological progression per RECIST v1.1, in both the PD-L1 ≥ 1% and ITT populations. Other secondary endpoints include objective response rate, duration of response, PFS rates (defined as time from randomization until earliest progression event) in both the PD-L1 ≥ 1% and ITT populations, safety/tolerability, and patient-reported outcomes. OS will be assessed using a stratified log-rank test adjusting for stratification factors. A stratified Cox proportional hazards model will estimate the hazard ratio and associated 95% confidence interval. Enrollment started in December 2025 and is ongoing across Asia, Australia, Europe, and the Americas. Clinical trial information: NCT07221253 .