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Evorpacept (ALX148) is a high-affinity signal regulatory protein alpha (SIRPα) fusion protein designed to block the CD47 checkpoint on cancer cells, thereby neutralizing the 'do-not-eat-me' signal and enabling macrophage-mediated phagocytosis. In this specific clinical context at M.D. Anderson Cancer Center, evorpacept is being evaluated in an investigator-initiated Phase I/II trial (NCT05025800) in combination with rituximab, a CD20-targeting monoclonal antibody, and lenalidomide, an immunomodulatory imide drug (IMiD). This triplet combination therapy is intended to treat patients with various subtypes of B-cell non-Hodgkin lymphoma, including follicular lymphoma, marginal zone lymphoma, and mantle cell lymphoma, by leveraging the synergistic effects of CD47 blockade, antibody-dependent cellular cytotoxicity (ADCC), and immunomodulation to enhance anti-tumor immune responses.
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