Cinrebafusp alfa + tucatinib

Cinrebafusp alfa + tucatinib is an investigational combination therapy being studied for the treatment of HER2-expressing gastric and gastroesophageal junction cancers. Cinrebafusp alfa (also known as PRS-343) is a bispecific fusion protein that targets both Tumor necrosis factor receptor superfamily member 9 (4‑1BB), a costimulatory receptor on T cells, and Receptor tyrosine-protein kinase erbB‑2 (HER2), a receptor overexpressed in certain tumors. It consists of 4-1BB-targeting Anticalin proteins fused to a HER2-targeting antibody, designed to promote T-cell activation specifically at the tumor site by bridging T cells with HER2-positive tumor cells[3][7][8]. Tucatinib is an oral small molecule tyrosine kinase inhibitor that selectively inhibits the human epidermal growth factor receptor 2 (HER2), blocking downstream signaling pathways involved in cancer cell proliferation and survival[1][5][6]. The combination aims to enhance anti-tumor immune responses by increasing surface HER2 expression (via tucatinib) and stimulating local T-cell activity (via cinrebafusp alfa)[8]. This regimen is currently under phase 2 clinical investigation for patients with HER2-low expressing gastric or gastroesophageal junction adenocarcinoma[4].

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