Subcutaneous Mosunetuzumab Shows Efficacy and Safety Among Elderly, Chemotherapy-Ineligible Patients With DLBCL: MorningSun Trial
Key Clinical Summary
- Population and Design: Phase 2 MorningSun trial (NCT05207670) enrolled 49 patients with newly diagnosed aggressive B-cell lymphoma (DLBCL n=36; high-grade n=6) who were ≥80 y or 65 to 79 y CIT-ineligible; median age 82.5 y, 53.1% IPI 3–5.
- Efficacy: At 12.5-month median follow-up, ORR 73.5%, CR 59.2%, 12-month PFS 68.8%, OS 77.2%; MRD negativity 68.8% among evaluable CRs, supporting durable, deep responses with fixed-duration monotherapy.
- Safety: Grade 1 injection-site reactions (51%) were most common; grade ≥3 AEs 65.3% (notably infections 16.3%, neutropenia 10.2%). Mosunetuzumab SC showed manageable toxicity and outpatient feasibility for elderly or frail DLBCL patients.
According to research presented by Jeff Sharman, MD, SCRI at Willamette Valley Cancer Institute & Research Center, The US Oncology Network, Eugene, Oregon, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida, fixed-duration subcutaneous (SC) mosunetuzumab monotherapy is efficacious and well-tolerated among elderly or chemoimmunotherapy (CIT)-ineligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Previous research has found mosunetuzumab to show promising efficacy for patients with DLBCL. Researchers conducted the phase 2 MorningSun trial (NCT05207670) to determine the efficacy of mosunetuzumab among patients who were over the age of 80 years or those aged 65 to 79 who were ineligible for chemoimmunotherapy.
The study enrolled 49 patients were included, of which 36 had DLBCL, 6 had high-grade B-cell lymphoma, and the remainder had rare aggressive histologies. The median age of all patients was 82.5 years (range, 71 to 101), and 53.1% of patients had an International Prognostic Index (IPI) score of 3 to 5.
At a median follow-up of 12.5 months (range, 1.4 to 30.8), the median number of cycles received was 14 (range, 1 to 17). The median time to response was 2.7 months. The 12-month progression-free survival (PFS) rate was 68.8% (95% confidence interval [CI], 52.1 to 80.6), and the overall survival (OS) rate was 77.2% (95% CI, 61.1 to 87.3). The overall response rate (ORR) was 73.5%, including a complete response (CR) rate of 59.2%. The median duration of response (DOR) and duration of CR (DOCR) were 84.6% and 95.0%, respectively.
Among patients who achieved a CR and were evaluable for minimal residual disease (MRD), 68.8% were MRD-negative.
In terms of safety, grade 1 injection site reactions were the most common adverse event (51.0%). Grade ≥3 adverse events occurred in 65.3% of patients, with infections (16.3%) and neutropenia (10.2%) being the most common.
The researchers concluded, “Interim data from MorningSun demonstrate that fixed-duration Mosun SC monotherapy is active in these patients, with promising efficacy and a manageable safety profile, with predominantly mild-to-moderate AEs, allowing for outpatient administration in the community practice setting.”
Source:
Sharman J, Tun A, Bisneto JV, et al. Fixed treatment duration subcutaneous mosunetuzumab monotherapy in elderly/unfit patients with previously untreated diffuse large B-cell lymphoma: Interim results from the Phase II MorningSun study. Dec 6-9, 2025; Orlando, FL. Abstract: 62
