Efficacy data revealed that after a median follow-up of 18.2 months, the overall response rate among 36 patients treated with the investigational agent was 77.8%.
Mosunetuzumab-axgb (Lunsumio) displayed clinically meaningful and durable responses among a dedicated cohort of patients with previously untreated marginal zone lymphoma (MZL), according to findings from the open-label phase 2 MorningSun trial (NCT05207670) that were presented at the 2025 Society of Hematologic Oncology Annual Meeting (SOHO).
Efficacy data revealed that after a median follow-up of 18.2 months (range, 1.5-30.4), the overall response rate (ORR) among 36 patients treated with the investigational agent was 77.8%. Additionally, 64% of patients in this cohort experienced a complete response (CR), with an additional 14% experiencing partial responses (PRs). Furthermore, CR rates across numerous high-risk subgroups, including those with elevated lactate dehydrogenase (LDH) levels, those with extranodal involvement, those 65 years and older, as well as those with stage III/IV Ann Arbor disease, were consistent with the overall population; the respective CR rates were 46%, 64%, 58%, and 48%.
Furthermore, among 30 patients with an evaluable tumor response, the median time to response was 2.8 months (range, 2.4-5.4), with 23 patients (63.9%) still experiencing a complete metabolic response (CMR) at the time of analysis. The median duration of response (DOR) and duration of complete response (DOCR) were both not reached (NR; 95% CI, not evaluable [NE]-NE), and the 12-month DOR and DOCR event-free rates were 92.3% and 100%, respectively.
The median progression-free survival (PFS) was NR (95% CI, NE-NE), and the respective 6- and 12-month PFS event-free rates were 90.5% (95% CI, 73.4%-96.8%) and 83.6% (95% CI, 64.8%-92.8%).
“This is the first study of mosunetuzumab to include a dedicated cohort of patients with previously untreated MZL,” Tara Graff, MD, hematologic oncologist and director of clinical research at Mission Blood and Cancer in Des Moines, Idaho, said in the oral presentation. “Clinically meaningful ORR of [77.8%] and a CMR of [63.9%] were seen. Durable responses were observed with 18.2 months of median follow-up. Safety and [cytokine release syndrome (CRS)] profiles were manageable, demonstrating that [subcutaneous] mosunetuzumab can be administered in the US community practices and outpatient settings.”
Patients with previously untreated symptomatic MZL with an ECOG performance status of 0 to 2 were enrolled on trial and received subcutaneous mosunetuzumab for up to 17 cycles, 21 days each, in the absence of disease progression or unacceptable toxicity. To mitigate CRS, mosunetuzumab was given as a 5 mg step-up dose on day 1 of cycle 1 followed by 45 mg on day 15. Thereafter, subsequent cycles consisted of 45 mg of the agent on day 1, with corticosteroid prophylaxis mandatory in cycles 1 and 2, but optional in subsequent cycles.
Those enrolled on the trial had a median age of 69 years (range, 36-81), 66.7% were female, and 88.9% were White. A total of 77.8% of patients had extranodal involvement, 19.4% had bulky disease, and 55.6% had an ECOG performance score of 0. Furthermore, 55.6% had Ann Arbor stage IV disease, with 30.6% and 16.7% having elevated LDH and B symptoms, respectively.
The primary end point of the trial was investigator-assessed ORR by Lugano criteria. Key secondary end points included PFS, DOR, DOCR, time to response, and safety.
The time of analysis no patients were undergoing ongoing treatment with mosunetuzumab; 58.3% had completed the study regimen and 41.7% discontinued treatment. The reasons for discontinuation included adverse effects (AEs; 16.7%), disease progression (8.3%), investigator decision (8.3%), and patient withdrawal (5.6%). The median number of cycles received was 17 (range, 1-17), and the median treatment duration was 51.0 weeks (range, 4-58).
All patients experienced at least 1 AE, with grade 3/4 AEs occurring in 63.9% of patients. The most common AEs included injection site reaction, fatigue, diarrhea, neutropenia/neutrophil count decreased, and CRS. The most common grade 3/4 AEs were decreased neutropenia/neutrophil count (27.8%) and anemia (11.1%).
No grade 5 AEs or immune effector cell-associated neurotoxicity syndrome (ICANS) incidences were observed. Additionally, serious AEs occurred in 38.9% of patients. Any-grade CRS occurred in 36.1% of patients, all of which were either grade 1 (22.2%) or 2 (13.9%) in severity and resolved. The median time to CRS was 2 days (range, 1-5), with a median duration of 2.5 days (range, 1-7).
Reference
Graff T, Burke JM, Tun AM, et al. IBCL-1494: MorningSun: open-label phase 2 trial of the efficacy and safety of subcutaneous mosunetuzumab as frontline treatment in symptomatic patients with marginal zone lymphoma (MZL). Presented at: 2025 SOHO Annual Meeting; September 3-6, 2025; Houston, TX. Abstract INCL-1494.