aplitabart + birinapant

**Aplitabart + birinapant** is a combination therapy under investigation for cancer, primarily solid tumors and colorectal cancer. **Aplitabart (IGM-8444)** is an engineered IgM monoclonal antibody that acts as a **DR5 (Death receptor 5/TRAIL receptor 2) agonist**, inducing apoptosis in cancer cells by activating the extrinsic apoptotic pathway. **Birinapant** is a small molecule **SMAC mimetic** that inhibits Inhibitor of Apoptosis Proteins (IAPs), promoting apoptosis through caspase activation. The rationale for combining these agents is that aplitabart sensitizes tumor cells to apoptosis via DR5 activation, while birinapant further lowers the threshold for apoptosis by antagonizing cellular survival signals mediated by IAPs. This dual mechanism aims for synergistic cytotoxicity and enhanced anti-tumor responses, as observed in preclinical models. The combination is being evaluated in the context of advanced solid tumors, including metastatic colorectal cancer, often in combination with chemotherapy backbones such as FOLFIRI and bevacizumab[1][2][5][6][7].

Other names

IGM-8444 + birinapant