Rilvegostomig (PD-1/TIGIT bispecific) + gemcitabine/cisplatin lifts mPFS to 8.3 months in front-line biliary tract cancer

Rilvegostomig, an IgG1 bispecific antibody simultaneously blocking PD-1 and TIGIT, was combined with standard gemcitabine 1000 mg/m² + cisplatin 25 mg/m² (Days 1, 8 Q3W) in the Phase 2 GEMINI-Hepatobiliary substudy 2 (NCT05775159). Thirty previously untreated unresectable/metastatic BTC patients (83% metastatic; PD-L1 ≥ 1% in 60%) received rilvegostomig Q3W for up to 2 years. Investigator-assessed 6-month PFS reached 73% and median PFS was 8.3 months (9.4 mo in PD-L1-positive tumors); ORR was 31% with a 6.9-month median DoR. Any-grade and grade ≥3 AEs occurred in 100% and 87% of patients, but rilvegostomig-related grade ≥3 events were limited to 13%, and only one patient discontinued therapy. For context, durvalumab (an antibody targeting PD-L1) + gem/cis, the current immuno-chemo standard, delivers a median PFS of 7.2 months and a 26.7% ORR with 76% grade 3/4 toxicity in advanced biliary tract cancers in the TOPAZ-1 trial (NCT03875235).