A Pilot Study Of Galunisertib (Ly2157299 Monohydrate) Plus Stereotactic Body Radiotherapy (Sbrt) In Advanced Hepatocellular Carcinoma (Hcc).

270Background: TGF-β, the strongest known immunosuppressive cytokine, modulates the hepatic immune response to various antigens and to ionizing radiation. When activated, TGF-β blocks the effector T-cell response to cellular destruction and the release of tumor-specific antigens. Preclinical data demonstrate that neutralizing TGF-β during radiation effectively generates a CD8+ T-cell response to multiple endogenous tumor antigens, thereby generating an in-situ vaccine against a tumor. We hypothesized that the combination of TGF-β receptor inhibition plus SBRT would produce a potent and clinically effective antitumor immune response against HCC. Methods: Patients received galunisertib (LY2157299 monohydrate) on days 1-14 of each 28 day cycle. SBRT was delivered in a single fraction of 18 Gy between days 15-28 of C1. Pre-treatment and on-treatment biopsies were obtained, as well as serial blood collections for CTCs, ctDNA and PBMCs. Results: 15 patients with advanced HCC and Child’s Pugh A cirrhosis were tr...