Figure 6.
On-treatment pharmacodynamics in PB and BM aspirates support the expected MoA of a TCB. (A) Cytokine dynamics with estimated mean change from baseline across all patients with valid data at a given time point. The error bars indicate the 95% confidence interval, and dashed lines indicate RO7283420 administration. (B) Scatter plots showing the cumAUC vs log2-transformed change from baseline of soluble CD25 (IL2SR) and CXCL10 plasma levels at the end of cycle 1 (FDR-adjusted P value <.1; Brownian distance covariance test). Dose scheme group with flat, SSU, and DSU indicated. (C,E) Heatmap of immunophenotype on-treatment changes in PB (C) and BM aspirates (E) of absolute cell counts per μL shown as the log2-transformed fold change (log2[FC]) from baseline. Significantly changed immunophenotypes are labelled with an x (unadjusted P value <.05; linear mixed-effects model [C]; paired t test for C3D1 vs baseline comparison [E]). Baseline value (cells/μL) for each marker is indicated by the color gradient, and immune cell subtypes are indicated by the color coding. Grey cells indicate data that are not available. All time points are samples drawn before the dose administration of the indicated cycle. (D,F) Volcano plots of immunophenotype on-treatment vs baseline changes of absolute cell counts/μL in PB (D) and BM (F) shown as effect size vs –log10 transformed P values (–log[pval]). Effect size is the estimated mean fold change from baseline (D) and Cohen’s D statistic at C3D1 vs baseline (F). Significantly expanded CD4+ and CD8+ T-cell populations are highlighted (unadjusted P value <.05 indicated by dashed horizontal line; linear mixed-effects model [D]; paired t test [F]). Cell subtypes are indicated by color coding. cumAUC, cumulative area under the curve; CxDx, Cycle x Day x; CM, central memory; CXCL10, C-X-C motif chemokine ligand 10; EM, effector memory; EMRA, terminally differentiated effector memory cells re-expressing CD45RA; FC, fold change; FDR, false discovery rate; IFNG, interferon gamma; INTLK, interleukin; MoA, mechanism of action; NK, natural killer; pre, pre-dose; post, post-dose 2 hours end of infusion; TCB, T-cell bispecific antibody; TNF, tumor necrosis factor; Treg, regulatory T cell.

On-treatment pharmacodynamics in PB and BM aspirates support the expected MoA of a TCB. (A) Cytokine dynamics with estimated mean change from baseline across all patients with valid data at a given time point. The error bars indicate the 95% confidence interval, and dashed lines indicate RO7283420 administration. (B) Scatter plots showing the cumAUC vs log2-transformed change from baseline of soluble CD25 (IL2SR) and CXCL10 plasma levels at the end of cycle 1 (FDR-adjusted P value <.1; Brownian distance covariance test). Dose scheme group with flat, SSU, and DSU indicated. (C,E) Heatmap of immunophenotype on-treatment changes in PB (C) and BM aspirates (E) of absolute cell counts per μL shown as the log2-transformed fold change (log2[FC]) from baseline. Significantly changed immunophenotypes are labelled with an x (unadjusted P value <.05; linear mixed-effects model [C]; paired t test for C3D1 vs baseline comparison [E]). Baseline value (cells/μL) for each marker is indicated by the color gradient, and immune cell subtypes are indicated by the color coding. Grey cells indicate data that are not available. All time points are samples drawn before the dose administration of the indicated cycle. (D,F) Volcano plots of immunophenotype on-treatment vs baseline changes of absolute cell counts/μL in PB (D) and BM (F) shown as effect size vs –log10 transformed P values (–log[pval]). Effect size is the estimated mean fold change from baseline (D) and Cohen’s D statistic at C3D1 vs baseline (F). Significantly expanded CD4+ and CD8+ T-cell populations are highlighted (unadjusted P value <.05 indicated by dashed horizontal line; linear mixed-effects model [D]; paired t test [F]). Cell subtypes are indicated by color coding. cumAUC, cumulative area under the curve; CxDx, Cycle x Day x; CM, central memory; CXCL10, C-X-C motif chemokine ligand 10; EM, effector memory; EMRA, terminally differentiated effector memory cells re-expressing CD45RA; FC, fold change; FDR, false discovery rate; IFNG, interferon gamma; INTLK, interleukin; MoA, mechanism of action; NK, natural killer; pre, pre-dose; post, post-dose 2 hours end of infusion; TCB, T-cell bispecific antibody; TNF, tumor necrosis factor; Treg, regulatory T cell.

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