Phase 2 durvalumab PD-L1 inhibitor plus histotripsy non-thermal focused ultrasound ablation in iCCA

This single-group Phase 2 pilot study (CODAH) at the University of Wisconsin–Madison evaluates whether adding histotripsy to ongoing maintenance durvalumab increases anti-tumor immune activation and remains safe in advanced, unresectable intrahepatic cholangiocarcinoma (iCCA). Durvalumab (Imfinzi; AstraZeneca) is a PD-L1 (CD274)–blocking monoclonal antibody intended to restore T-cell activity by releasing an immune checkpoint brake, while the HistoSonics Edison System uses non-invasive, non-thermal focused ultrasound (histotripsy) to mechanically disrupt targeted liver tumor tissue, potentially turning the ablated lesion into an “in situ vaccine.” Patients must have disease control after ~18 weeks of first-line gemcitabine/cisplatin-based chemoimmunotherapy including durvalumab, then continue durvalumab maintenance with a scheduled histotripsy treatment and paired research biopsies (pre- and ~14 days post-histotripsy) to measure immune changes. The commercial/scientific angle is combining a device-based local tumor destruction platform (HistoSonics; collaborator) with checkpoint maintenance to amplify immune infiltration signals in a tumor type where durable responses to immunotherapy alone are uncommon. Today’s care for unresectable/advanced biliary tract cancer is first-line gemcitabine + cisplatin + durvalumab followed by durvalumab maintenance, then molecularly matched targeted therapy when actionable alterations are present (for example FGFR2 fusions or IDH1 mutations) or second-line chemotherapy.