Phase 1 axatilimab CSF1R-blocking monoclonal antibody conditions macrophages alongside commercial CAR-T.

This open-label Phase 1 study (“MAC-SHIFT”) at Northside Hospital evaluates whether adding axatilimab—a CSF1R-directed monoclonal antibody that inhibits macrophage/monocyte CSF-1R signaling and can reduce proinflammatory, tissue macrophage activity—can improve outcomes around commercially available CAR-T therapy in high-risk large B-cell lymphoma (LBCL). Patients receive axatilimab plus a commercial CAR-T product (the CAR-T component is an autologous chimeric antigen receptor T-cell therapy designed to recognize a B-cell antigen such as CD19, depending on the commercial product selected). The core angle is tumor-microenvironment “macrophage conditioning” to potentially enhance CAR-T expansion, persistence, and depth/durability of response in biologically or clinically high-risk LBCL, where relapse after CAR-T remains a key unmet need. Today’s care for high-risk relapsed/refractory LBCL typically includes salvage chemoimmunotherapy and/or antibody-based options as bridges, followed by CD19 CAR-T in eligible patients, with bispecific antibodies increasingly used in later lines; this trial tests whether targeted CSF1R blockade can make CAR-T work better rather than replacing it.