First-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): Primary analysis of GEMINI-Hepatobiliary substudy 2 Cohort A.

4080 Background: Immune checkpoint inhibitors plus CTx have improved outcomes in first-line advanced BTC (median progression-free survival [PFS] 6.5–7.2 months), but survival remains limited. Rilve, an anti-PD-1/TIGIT bispecific antibody, may provide benefit by targeting two immune checkpoints. GEMINI-Hepatobiliary (NCT05775159) is a phase 2 study evaluating rilve or volrustomig alone or in combination regimens in patients (pts) with advanced hepatocellular carcinoma (substudy 1) or BTC (substudy 2). We report data from Cohort A (rilve plus CTx) in substudy 2. Methods: Pts aged ≥18 years with previously untreated unresectable/metastatic BTC and an ECOG performance status 0–1 received rilve every 3 weeks (Q3W) for up to 2 years plus gemcitabine 1000 mg/m 2 and cisplatin 25 mg/m 2 on days 1 and 8 Q3W for up to 8 cycles. Coprimary endpoints were investigator-assessed 6-month PFS per RECIST v1.1 and safety and tolerability; secondary endpoints included median PFS, objective response rate (ORR), duration of response (DoR; all investigator-assessed per RECIST v1.1), and pharmacokinetics (PK). Tumoral PD-L1 expression, peripheral PD-1 and TIGIT receptor occupancy (RO), and T cell profiles were also evaluated. Results: Thirty pts were treated; median age was 60 years, 70.0% were Asian, and 83.3% had metastatic disease. As of Nov 4 2024, the median follow-up in all pts was 6.9 months (interquartile range 5.6–9.5) and rilve treatment was ongoing in 36.7% of pts. Efficacy and safety data are shown in the Table. The 6-month PFS rate was 73.0%; median PFS was 8.3 months. Median PFS was numerically longer in pts with PD-L1 tumor area positivity ≥1% (9.4 months, n = 18) vs the overall study population. The safety profile was manageable and consistent with prior studies. Rilve exposure was consistent with historical monotherapy data, indicating an absence of PK drug interactions and cross-indication differences. Rilve achieved ≥90% PD-1 and TIGIT RO on peripheral T cells and induced peripheral T cell proliferation. Conclusions: Rilve plus CTx demonstrated promising efficacy with a manageable safety profile and sustained target engagement. Longer follow-up for data maturity is warranted. Phase 3 studies with rilve in BTC (ARTEMIDE-Biliary 01; DESTINY-BTC01) are ongoing. Clinical trial information: NCT05775159 . N=30* PFSEvents in all dosed pts, n (%)6-month rate, % (95% CI)Median, months (95% CI) 19 (63.3)73.0 (53.2–85.5)8.3 (6.7–9.6) ORR, % (95% CI) 31.0 (15.3–50.8) Best overall response, n (%)Partial responseStable diseaseProgressive disease 9 (31.0)18 (62.1)2 (6.9) Median DoR, months (95% CI) 6.9 (2.8–not calculated) Any / rilve-related AEs, n (%)Grade ≥3Serious AEsLeading to rilve discontinuationLeading to death 30 (100) / 21 (70.0)26 (86.7) / 4 (13.3)12 (40.0) / 2 (6.7)1 (3.3) / 02 (6.7) / 0 *N=29 for response outcomes. AE, adverse event; CI, confidence interval.