Fixed-Duration Subcutaneous Mosunetuzumab Achieves High Response Rates and PK Non-Inferiority in Relapsed or Refractory Follicular Lymphoma

Presented by

Volker Wibking, MD , Genentech, CA, USA

Conference

SOHO 2025

A phase 2 study shows that fixed-duration subcutaneous (SC) mosunetuzumab provides high and durable response rates with a manageable safety profile in relapsed or refractory (R/R) follicular lymphoma (FL), while demonstrating pharmacokinetic (PK) non-inferiority compared with intravenous (IV) administration.

The study (NCT02500407) enrolled 94 patients with grade 1-3a FL who had received ≥2 prior therapies. Mosunetuzumab was given SC in 21-day cycles with step-up dosing in cycle 1 (5 mg day 1, 45 mg days 8 and 15, then 45 mg on day 1 of subsequent cycles). Treatment duration was fixed, and the primary objective was to establish PK non-inferiority to IV mosunetuzumab, using serum trough concentration at cycle 3 and AUC0-84 as co-primary endpoints. On behalf of his colleague and first author, Nancy Bartlett, MD (Washington University, St Louis, MO), Volker Wibking, MD (Genentech, South San Francisco, CA), presented these results at the 13th Society of Hematologic Oncology (SOHO) 2025 Annual Meeting in Houston, TX [1].

PK non-inferiority was met, with geometric mean ratios (GMRs) of 1.39 (90% CI 1.2-1.6) for Ctrough(C3) and 1.06 (90% CI, 0.9-1.2) for AUC0–84, confirming equivalent systemic exposure. The overall response rate (ORR) was 77% and the complete response (CR) rate was 62%, as assessed by independent review. Estimated 18-month duration of response and duration of CR were 64% (95% CI 52.1-76.1) and 70% (95% CI 57.1-82.3), respectively. Median progression-free survival was 23.7 months (95% CI 14.6-not estimable), and median overall survival was not reached.

Safety findings were consistent with previous mosunetuzumab studies. Injection-site reactions (ISRs) occurred in 61% of patients, fatigue in 35%, and cytokine release syndrome (CRS) in 30%. ISRs were all grade 1/2 and non-serious, with none leading to treatment discontinuation. CRS events were predominantly low grade (28% grade 1/2, 2% grade 3), occurred only in cycle 1, and all resolved. Serious CRS was reported in 16% of patients.

These results confirm that SC mosunetuzumab achieves PK equivalence to the IV formulation and delivers high rates of deep and durable responses in heavily pretreated FL, with a favourable safety profile that supports outpatient use. The convenience of fixed-duration, SC administration positions mosunetuzumab as a practical alternative to IV delivery in this setting.

Barlett N, et al. Fixed-Duration Subcutaneous Mosunetuzumab Mosun SC) Leads to High Rates of Durable Responses, Low Rates of Cytokine Release Syndrome (CRS), and Non-Inferior Exposure Compared With Intravenous Administration in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma (FL): Primary Analysis of a Pivotal Phase 2 Study. Abstract IBCL-482, SOHO 2025, 2- 7 September 2025.

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