Evaluation of the combinatorial effect of glofitamab with R-CHOP and R-CHP-Pola. (A) Experimental design of an in vivo efficacy study. Humanized BRGS-CD47 mice with SC SU-DHL-8 tumors were allocated to 7 experimental groups (14 mice per group) and were treated with either vehicle (histidine buffer), Pola (1 mg/kg), step-up dosing (SUD) of glofitamab (0.15-0.5 mg/kg), R-CHOP (rituximab 30 mg/kg, cyclophosphamide 30 mg/kg, doxorubicin 2.5 mg/kg, vincristine 0.375 mg/kg, methylprednisolone 0.12 mg/kg), R-CHP-Pola (rituximab 30 mg/kg, cyclophosphamide 30 mg/kg, doxorubicin 2.5 mg/kg, methylprednisolone 0.12 mg/kg, Pola 1 mg/kg), or a combination of glofitamab with either staggered R-CHOP or R-CHP-Pola using the same dosing as in monotherapy groups. Treatments were administered IV according to the displayed timeline. Methylprednisolone (P) was injected IV on 3 consecutive days during each cycle of R-CHOP or R-CHP-Pola treatment. Four scout animals per group were taken on day 17 for ex vivo analysis, and the study was terminated on day 31. (B) Representative immunohistochemistry (IHC) staining for human CD19, CD20, CD79b, and CD3 in untreated SU-DHL-8 tumors. (C) Average tumor volumes are illustrated as mean + SEM for all treatment groups over time. Tumor-free mice are indicated as x/10. (D) Time-to-event analysis for all treatment groups, with a cutoff at a tumor volume of 1000 mm³. Median survival values are presented as days after tumor cell injection. (E) Body weight kinetics are illustrated as mean + SEM. (F) Analysis of normalized B-cell frequencies in the blood and spleen and T-cell frequencies in the blood and tumors, assessed via flow cytometry on study day 17. Bars represent the mean + SEM, and individual dots represent values from individual mice. Statistical analysis was performed using 1-way analysis of variance (ANOVA), and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. SC, subcutaneous; SEM, standard error of the mean.