Fixed‐Duration Subcutaneous Mosunetuzumab in Relapsed/Refractory Follicular Lymphoma: Pivotal Phase 2 Primary Analysis

Mosunetuzumab is approved as an intravenous (IV) formulation for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior therapies. A subcutaneous (SC) formulation, aiming to improve patient safety and convenience, has been developed. We report the primary analysis of pharmacokinetics (PK), efficacy, and safety of mosunetuzumab SC (N = 94; median follow-up: 26.1 months) at the recommended Phase 2 dose (Cycle [C]1 Day [D]1: 5 mg; C1D8 and D15, and C2D1 onwards: 45 mg) in patients with R/R FL after ≥ 2 prior therapies, alongside data from a within-study comparator cohort of mosunetuzumab IV in a similar patient population (N = 90; median follow-up: 22.5 months). The co-primary PK endpoints (C_trough and AUC) were met, demonstrating non-inferior exposure of mosunetuzumab SC versus IV (observed C_trough[C3]: geometric mean ratio [GMR] 1.39 [90% confidence interval (CI): 1.20-1.61]; AUC_0-84: GMR 1.06 [90% CI: 0.92-1.21]). Mosunetuzumab SC efficacy was consistent with IV: overall response rate, 76.6% (95% CI: 66.7-84.7); complete response rate, 61.7% (95% CI: 51.1-71.5); median duration of complete response, 34.6 months (95% CI: 20.7-not evaluable [NE]); and median progression-free survival, 23.7 months (95% CI: 14.6-NE). Mosunetuzumab SC demonstrated a favorable safety profile versus mosunetuzumab IV with a numerically lower rate (29.8% vs. 44.4%) and severity (grade ≥ 2: 9.6% vs. 18.9%) of cytokine release syndrome (CRS) events. Mosunetuzumab SC combines the benefits of short administration time, fixed-duration treatment, outpatient accessibility, and low CRS rate, offering clinically meaningful improvements in patient convenience and safety. Trial Registration: www.clinicaltrials.gov: NCT02500407.