Phase 2 mosunetuzumab CD20×CD3 bispecific antibody T‑cell engager for MRD+ CLL/SLL

This MD Anderson Cancer Center, open-label, single-group Phase 2 study tests whether adding mosunetuzumab—a CD20×CD3 T‑cell–engaging bispecific antibody from Genentech/Roche—can eradicate measurable residual disease (MRD) in high-risk CLL/SLL patients who have persistent MRD despite being on continuous Bruton tyrosine kinase inhibitor (BTKi) therapy. Patients must have had at least 2 prior systemic lines and be on a covalent or non-covalent BTKi for at least 12 months, with bone marrow MRD positivity at 10^-4 sensitivity by clonoSEQ; the trial also excludes high disease burden (e.g., larger nodes or high ALC), reflecting a strategy to apply T‑cell redirection when tumor burden is low to reduce cytokine release risk. Mosunetuzumab uses step-up dosing, with the first 6 participants dosed inpatient during Cycle 1 as a safety lead-in, and subsequent participants treated outpatient. The primary endpoint is the bone marrow undetectable MRD4 rate at the end of Cycle 17, with a stated target of 50%, plus durability and treatment-stop feasibility as key secondary angles. Today’s care for multiply relapsed/high-risk CLL after BTKi exposure commonly includes switching to venetoclax-based regimens, non-covalent BTK inhibition (e.g., pirtobrutinib), anti-CD20 antibodies in combinations, and cellular therapy in selected cases; this trial instead explores a fixed-duration, “off-the-shelf” T‑cell engager to deepen response and potentially allow stopping continuous BTKi therapy.