GEMINI-Hepatobiliary: A phase 2 study of novel first-line immuno-oncology-based treatments in patients with advanced hepatobiliary cancers.

TPS4187 Background: Although targeted therapies and immuno-oncology (IO)-based regimens have improved overall survival (OS) in advanced hepatobiliary carcinomas, long-term survival rates remain unsatisfactory. Early-phase studies have demonstrated the efficacy of volrustomig (volru; anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody mAb) in patients (pts) with non-small-cell lung cancer (NSCLC) and renal cell carcinoma, and of rilvegostomig (rilve; anti-PD-1/TIGIT bispecific humanized IgG1 mAb) in pts with NSCLC, along with manageable safety profiles. GEMINI-Hepatobiliary (NCT05775159) is a phase 2, open-label, multidrug, multicenter, master protocol study designed to evaluate the preliminary efficacy and safety of novel IO bispecific mAbs as monotherapy or in combination with standard of care anticancer agents in pts with advanced hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). Methods: The GEMINI-Hepatobiliary platform design permits separate independent substudies (Table). Substudy 1 includes treatment-naïve adults (≥18 years) with histologically confirmed advanced HCC not eligible for locoregional therapy, Barcelona Clinic Liver Cancer Stage B/C, Child-Pugh class A 5–6, and an ECOG performance status (PS) of 0–1. Pts will be treated with volru as monotherapy or in combination with bevacizumab or lenvatinib. Primary endpoints for Substudy 1 are safety and objective response rate (ORR) per RECIST v1.1 by investigator’s assessment. Substudy 2 includes treatment-naïve adults with locally advanced or metastatic, histologically confirmed BTC and an ECOG PS of 0–1. Pts will be treated with gemcitabine + cisplatin with either rilve or volru. Primary endpoints for Substudy 2 are safety and progression-free survival (PFS) per RECIST v1.1 by investigator’s assessment. Secondary endpoints for both substudies include duration of response, disease control rate, ORR, PFS, OS, pharmacokinetics, and immunogenicity. While there are no formal statistical comparisons or hypothesis testing, sample sizes were selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Asia, and Europe. GEMINI-Hepatobiliary master protocol design. Clinical trial information: NCT05775159 . Table: see text