Systems-based digital twins to help characterize clinical dose-response and propose predictive biomarkers in a Phase I study of bispecific antibody, mosunetuzumab, in NHL.

Abstract in brief

• The study uses a systems pharmacology model to create digital twins that represent individual patient variability in a Phase I trial of mosunetuzumab for NHL, helping to understand how different doses affect tumor response.
• Simulations show that higher drug exposure improves tumor reduction and that patients with indolent NHL are more sensitive to the drug due to lower tumor growth rates and T-cell infiltration; key biological factors influencing response include tumor size, proliferation rate, and T-cell presence.
• The model suggests that the anti-tumor T-cell response mainly involves expansion of existing T-cells within the tumor, rather than new T-cells entering from outside, providing insights into immune mechanisms driving treatment efficacy.]