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

ABSTRACT 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.