Phase 1b-2 trial of mosunetuzumab plus polatuzumab vedotin for relapsed or refractory aggressive large B cell lymphoma

Patients with relapsed or refractory aggressive large B cell lymphoma (R/R LBCL) have limited therapeutic options. A phase 1b-2 trial at 15 centers in the USA and Canada evaluated the second or later line combination of mosunetuzumab (a CD20xCD3 T-cell engaging bispecific antibody) and polatuzumab vedotin (an anti-CD70B antibody-drug conjugate) for with R/R LBCL. At data cutoff, 120 patients were enrolled (22 dose escalation, 98 dose expansion). The independent review committee-assessed best overall response rate was 59.2% (95% CI 48.8-69.0), meeting the primary end point, with complete response in 45.9% of patients. The figure shows duration of response and survival outcomes. Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0% of patients) and fatigue (6.7%), while any-grade cytokine release syndrome occurred in 16.7%. The authors conclude that the combination of mosunetuzumab an polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy for R/R aggressive LBCL.