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Keytruda + HBM4003 (pembrolizumab + porustobart) is an investigational combination immunotherapy regimen under clinical development for the treatment of advanced solid tumors, including microsatellite-stable (MSS) colon cancer and non-small cell lung cancer (NSCLC). The regimen combines pembrolizumab (Keytruda), a humanized monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor, with porustobart (HBM4003), a next-generation, fully human heavy-chain-only monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Porustobart is engineered with an enhanced Fc region to promote the depletion of immunosuppressive regulatory T cells (Tregs) in the tumor microenvironment via antibody-dependent cellular cytotoxicity (ADCC), while pembrolizumab prevents PD-1 from binding to its ligands (PD-L1 and PD-L2) to restore T-cell activation. By simultaneously targeting these complementary immune checkpoint pathways, the combination aims to synergistically enhance anti-tumor immune responses. Solstice Oncology is developing the combination in the neoadjuvant setting for resectable stage II-III MSS colon cancer under a license from Harbour BioMed.
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