First-line rilvegostomig (R) + chemotherapy (CTx) in advanced biliary tract cancer (BTC): Updated analysis of GEMINI-Hepatobiliary substudy 2 cohort A.

Abstract

4105 Background: Addition of PD-(L)1 inhibitors to CTx has transformed advanced BTC treatment but survival is limited for most patients (pts). R is a monovalent, Fc-reduced PD-1xTIGIT bispecific antibody that delivers coordinated and synchronous PD-1 and TIGIT blockade on immune effector cells. The primary analysis of substudy 2 Cohort A of GEMINI-Hepatobiliary (NCT05775159), a global phase 2 study evaluating R + CTx in pts with advanced BTC, demonstrated promising efficacy and a manageable safety profile. We report updated analyses after ≥18 months of follow-up for the last enrolled pt. Methods: Pts ≥18 years with previously untreated unresectable/metastatic BTC and ECOG PS 0/1 received intravenous R every 3 weeks (Q3W; ≤2 years) + gemcitabine 1000 mg/m 2 + cisplatin 25 mg/m 2 on days 1 and 8 Q3W (≤8 cycles). Coprimary endpoints were 6-month progression-free survival (PFS) and safety/tolerability. Secondary endpoints included median PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and overall survival (OS). Response and progression were investigator-assessed per RECIST v1.1. Results: As of Oct 24, 2025, the median follow-up for OS was 16.2 months (IQR 10.4–21.5); 6 pts (20.0%) received ≥20 cycles of R. Median OS was 16.8 months (95% confidence interval [CI] 11.0–not calculable [NC]) overall; 18-month OS was 44.8% (95% CI 26.5–61.6). Median OS was > 13 months across all subgroups based on age ( < 65/≥65 years), ECOG PS (0/1), geography, initially unresectable/recurrent disease at enrollment, and primary tumor location (gallbladder or bile duct). Two unconfirmed responses were identified after > 85 weeks follow-up: one complete and one partial response. The safety profile was consistent with the primary analysis. The most common treatment-related adverse events (AEs) were anemia (53.3%), neutrophil count decreased (50.0%), and platelet count decreased (43.3%). Detailed efficacy and safety data are in the Table. Conclusions: R + CTx demonstrated promising efficacy and a manageable safety profile. This study and phase 3 studies of R in BTC (ARTEMIDE-Biliary01, ARTEMIDE-Biliary02, DESTINY-BTC01) are ongoing. Clinical trial information: NCT05775159 . N=30* PFS Events, n (%) 6-month, % (95% CI) 12-month, % (95% CI) Median (95% CI), months 25 (83.3)73.0 (53.2–85.5)25.6 (11.4–42.6)8.2 (6.7–11.1) Confirmed ORR, % (95% CI) 31.0 (15.3–50.8) Best objective response, n (%) Partial response Stable disease Progressive disease 9 (31.0)18 (62.1)2 (6.9) DCR, % (95% CI) 93.1 (77.2–99.2) DoR, median (95% CI), months 6.9 (2.8–NC) OS Events, n (%) 12-month, % (95% CI) 18-month, % (95% CI) Median (95% CI), months 19 (63.3)65.5 (45.4–79.7)44.8 (26.5–61.6)16.8 (11.0–NC) Any / R-related AEs, n (%) Grade ≥3 Serious Led to R discontinuation Led to death 30 (100) / 22 (73.3)27 (90.0) / 5 (16.7)14 (46.7) / 3 (10.0)2 (6.7) / 1 (3.3) † 2 (6.7) / 0 * N=29 for responses. † Hepatic function abnormal.