Biliary tract cancer (BTC) remains a challenging disease to manage, with current first-line treatment options offering limited survival benefits. Immune checkpoint inhibitors, when combined with chemotherapy, have improved outcomes in some cases, but median progression-free survival (PFS) typically ranges between 6.5 and 7.2 months. Rilvegostomig is a bispecific antibody aimed to enhance the antitumor immune response by targeting 2 key immune checkpoints, programmed cell death protein 1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains. This potentially offers a new avenue for improved clinical outcomes through the targeting of immune checkpoints. The GEMINI-Hepatobiliary study (NCT05775159) evaluated the efficacy and safety of rilvegostomig in combination with chemotherapy (gemcitabine and cisplatin) as a first-line treatment for patients with unresectable or metastatic BTC. This study was composed of 2 substudies, with the first (substudy 1) evaluating patients with hepatocellular carcinoma and the second (substudy 2) evaluating patients with advanced or metastatic BTC. Data described here are from cohort A in substudy 2.
Patients aged ≥18 years with previously untreated, unresectable, advanced or metastatic BTC and an ECOG performance status of 0 to 1 were administered rilvegostomig every 3 weeks for up to 2 years, in combination with gemcitabine and cisplatin for up to 8 cycles. The trial’s co-primary endpoints were 6-month PFS rate and safety and tolerability. Secondary endpoints included median PFS, disease control rate (DCR), objective response rate (ORR), duration of response (DOR), and pharmacokinetics. Exploratory analyses evaluated biomarkers such as programmed death-ligand 1 expression.
The study included 30 patients with advanced BTC who had not received prior treatment. The median age of the patients was 60 years. Seventy percent of patients were Asian, and 83.3% had metastatic disease. After a median follow-up of 6.9 months, the 6-month PFS rate was 73%, and the median PFS was 8.3 months. Overall survival data were not mature after a median follow-up of 9.8 months. The ORR was 31%, with 31% of patients achieving partial responses and 62.1% experiencing stable disease. The median DOR was 6.9 months, and the DCR at 24 weeks was 79.3%. Rilvegostomig exposure aligned with previously reported monotherapy data, suggesting no pharmacokinetic drug interactions or differences across indications.
The safety profile of rilvegostomig plus chemotherapy was manageable and consistent with prior studies. Although all patients experienced adverse events (AEs), 70% were related to rilvegostomig and included an increase in alanine aminotransferase (20.0%), rash (13.3%), and an increase in aspartate aminotransferase (10.0%). The most common treatment-related adverse event was anemia (53.3%), followed by a decrease in neutrophil count (50.0%), and a decrease in platelets (43.3%). Grade ≥3 AEs were reported in 86.7% of patients, with serious AEs occurring in 40%. A total of 13.3% grade ≥3 AEs were related to rilvegostomig, and 6.7% of serious AEs were related to rilvegostomig. Only 3.3% of patients discontinued rilvegostomig due to AEs.
This study demonstrates that rilvegostomig combined with chemotherapy has promising efficacy and a manageable safety profile in patients with advanced BTC. This represents a significant step forward in improving outcomes for patients with advanced BTC, a population with limited treatment options. The results warrant further exploration in larger phase 3 trials, such as ARTEMIDE-Biliary 01 and DESTINY-BTC01, which are currently ongoing.
Zhou J, Choi HJ, Ikeda M, et al. First-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): primary analysis of GEMINI-Hepatobiliary substudy 2 cohort A. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Poster 370.
To sign up for our newsletter or print publications, please enter your contact information below.
