galunisertib + ramucirumab

Combination of **galunisertib** (a small-molecule inhibitor of transforming growth factor beta receptor type I, TGF-βRI/ALK5) and **ramucirumab** (a monoclonal antibody targeting vascular endothelial growth factor receptor 2, VEGF-R2). This combination was developed to simultaneously inhibit TGF-β and VEGF signaling pathways, with the goal of reducing tumor angiogenesis, invasiveness, and immune evasion in advanced hepatocellular carcinoma (HCC). Preclinical rationale supported dual inhibition for synergistic anti-tumor effect, but clinical results showed that while the combination was safe and the recommended phase 2 dose was defined (galunisertib 150 mg orally twice daily, days 1–14 every 28 days; ramucirumab 8 mg/kg IV every 2 weeks), there was limited evidence of enhanced efficacy, leading to discontinuation of further clinical development as a combination[1][3][5].