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Nivolumab + ipilimumab + High Intensity Focused Ultrasound Histotripsy (HIFU-HT) is an investigational combination therapy being evaluated in the iFOCUS Phase 1 clinical trial at UMC Utrecht for the treatment of metastatic or unresectable cancer. This regimen combines two immune checkpoint inhibitors—nivolumab, a monoclonal antibody targeting the programmed death-1 (PD-1) receptor, and ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)—with HIFU-HT, a non-invasive medical device technology that uses focused ultrasound to mechanically disrupt tumor tissue (histotripsy). The goal of this combination is to enhance the systemic anti-tumor immune response by using HIFU-HT to release tumor antigens and create a pro-inflammatory environment, potentially overcoming resistance to immunotherapy in patients with metastatic or unresectable solid tumors that have progressed after standard treatment.
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