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**Onfekafusp alfa + doxorubicin** is a combination therapy under clinical development for the first-line treatment of advanced or metastatic soft tissue sarcoma. Onfekafusp alfa (also known as L19TNF or Fibromun) is a fully human antibody-cytokine fusion protein that targets the extra domain-B (EDB) of fibronectin in tumor vasculature, delivering tumor necrosis factor (TNF) directly to the tumor site. This results in apoptosis of tumor endothelial cells, vascular disruption, increased tumor permeability, and enhanced uptake of chemotherapeutic agents, with the intent of generating a synergistic anti-tumor effect. Doxorubicin is an established small molecule chemotherapy agent that intercalates DNA and inhibits topoisomerase II, thereby slowing or stopping cancer cell growth. The combination regimen aims to improve outcomes compared to doxorubicin alone and address the limited therapeutic options for patients ineligible for surgical resection.[1][2][3][4][5][7]
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