SC Mosunetuzumab Will Be Accessible for MZL Care in Community Settings

At the Society of Hematologic Oncology 2025 Annual Meeting, updated results from the phase 2 MorningSun trial (NCT02500407) showed that subcutaneous single-agent mosunetuzumab-axgb (Lunsumio) achieved meaningful, durable responses and was tolerable for patients with previously untreated marginal zone lymphoma (MZL).¹

As a basket trial, MorningSun was born after subcutaneous mosunetuzumab was proven to be noninferior to the intravenous formulation. Of the various disease types included in the trial, there is an unmet need for patients with MZL, as chemoimmunotherapy combinations are the current standard, and researchers seek more improvements.

Notably, mosunetuzumab is FDA-approved as an intravenous formulation in the third-line treatment of patients with relapsed/refractory follicular lymphoma.²

Tara M. Graff, DO, MS, the presenting author and director of Clinical Research at Mission Cancer and Blood, spoke with CancerNetwork® about these results and their implications on the MZL treatment paradigm.

Transcript:

What was the rationale for evaluating mosunetuzumab in MZL?

The rationale backing up the MorningSun trial is that, currently, mosunetuzumab is a CD3/CD20 bispecific antibody approved in relapsed/refractory follicular lymphoma in the third-line setting, and it’s approved in an [intravenous (IV)] formulation—there was a trial done that looked at studying mosunetuzumab in a [subcutaneous] formulation compared with IV to make sure that it was not inferior, and it proved not to be.² Then, with that, the MorningSun trial was born.

The MorningSun trial is basket trial looking at the mosunetuzumab subcutaneous formulation across a number of different disease subtypes, [including] follicular lymphoma, both low tumor burden and high tumor burden; you have MZL and all subtypes of MZL; and you have diffuse large B-cell lymphoma for the elderly unfit population. Those are all frontline treatments, so none of those patients have seen any therapy before.

You also have patients with relapsed/refractory mantle cell lymphoma, transformed lymphoma, and then Richter’s transformation. Specifically, there’s an unmet need for our patients with frontline [MZL]. Typically, we use a combination of chemoimmunotherapy, but we want to improve on that in the same way we are improving on other types of lymphoma. That [informed] that cohort in MorningSun.

What are the immediate clinical implications of these findings?

[Mosunetuzumab offers] a chemotherapy-free option for these patients. Nobody wants chemotherapy, and I’m not saying that chemotherapy is bad, but it’s just that we’ve advanced. We’ve advanced in diffuse large B-cell lymphoma and follicular lymphoma, and we’re making advancements all the time to be chemotherapy-free or use the least amount of chemotherapy as possible. [MZL], in terms of the indolent lymphomas, gets forgotten about sometimes. This is offering those patients a tolerable and efficacious [therapy], and it’s a finite amount of therapy; it’s 17 cycles, and then it’s done. They’re not on treatment consistently or constantly; it’s not “treat to progression”. It is 17 cycles, and then you’re done. They can stay home. They don’t have to go to the hospital. They don’t have to travel to another center. This was able to be done as an outpatient in community sites.

What will happen when it gets approved? Not every community site is going to be doing bispecific [antibodies]. We’re trying to get more availability of bispecific [antibodies] in the community. Hopefully, this therapy will make its way into as many sites as safely as possible, so we’ll see how it turns out.

References

1. Burke JM, Tun AM, Villasboas J, et al. MorningSun: open-label phase II trial of the efficacy and safety of subcutaneous mosunetuzumab as frontline treatment in symptomatic patients with marginal zone lymphoma. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, TX. Abstract IBCL-1494.
2. FDA grants accelerated approval to mosunetuzumab-axgb for relapsed or refractory follicular lymphoma. FDA. December 22, 2022. Accessed September 17, 2025. https://tinyurl.com/4munzr95