Mosunetuzumab for Marginal Zone Lymphoma

Overseen By Izidore Lossos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Izidore Lossos, MD

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: DLBCL, CNS lymphoma, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication called Mosunetuzumab (also known as Lunsumio) to determine its effectiveness for people with Extranodal Marginal Zone Lymphoma (EMZL), a type of lymphoma affecting areas outside the lymph nodes. Researchers aim to assess whether this treatment improves outcomes and is safe for patients. It targets individuals diagnosed with EMZL who have not yet received any cancer treatment and have the disease at any stage from I to IV. Those experiencing symptoms like weight loss, fever, night sweats, or enlarged lymph nodes may consider this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications, like prednisone over 20 mg, within 2 weeks before starting the trial. However, some medications, like inhaled corticosteroids or antibiotics for H. pylori, are allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Mosunetuzumab is likely to be safe for humans?

Research shows that mosunetuzumab has been tested for safety in people with certain types of lymphoma, including conditions similar to Extranodal Marginal Zone Lymphoma (EMZL). In earlier studies, mosunetuzumab proved to be very effective and generally well-tolerated. The overall response rate reached 77.8%, and many patients experienced a complete response, meaning their cancer was not detectable after treatment.

Importantly, the treatment had manageable side effects. While some side effects may occur, they are usually not severe and can be managed with medical help. The studies also provided long-term safety information, which is a positive sign for its use over time.

These findings offer a hopeful outlook for the safety of mosunetuzumab in treating EMZL. However, it is always important to consult a doctor to understand how this treatment might work personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for marginal zone lymphoma, such as chemotherapy or rituximab, Mosunetuzumab is unique because it is a bispecific antibody that simultaneously targets CD20 on B-cells and CD3 on T-cells. This dual-targeting mechanism helps to recruit the body's T-cells to attack and eliminate cancerous B-cells effectively. Researchers are excited about Mosunetuzumab because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients compared to traditional therapies.

What evidence suggests that Mosunetuzumab might be an effective treatment for Extranodal Marginal Zone Lymphoma?

Research has shown that Mosunetuzumab, which participants in this trial will receive, holds promise for treating lymphoma. In earlier studies, 77.8% of patients responded to the treatment, and 63.9% showed no signs of active cancer. On average, patients began to see results in just 2.8 months. These outcomes indicate that Mosunetuzumab can effectively help patients achieve remission and is generally safe, with manageable side effects. These findings offer particular hope for those with untreated marginal zone lymphoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Izidore Lossos, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for individuals with a type of cancer called Extranodal Marginal Zone Lymphoma (EMZL), who haven't been treated yet. It's open to those whose cancer ranges from stage I-IV, indicating various extents of disease spread.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

Able and willing to sign the informed consent form (ICF)

Life expectancy >3 months

Exclusion Criteria

My lymphoma has changed into a more aggressive form known as DLBCL.

I need immediate treatment to reduce my cancer cells.

History of severe allergic or anaphylactic reaction to specific antibodies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Mosunetuzumab for eight 21-day cycles

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab

Trial Overview The study is testing Mosunetuzumab, a new medication, to see if it can help treat EMZL effectively. The goal is to determine whether this drug improves patient outcomes and its safety profile.

How Is the Trial Designed?

Group I: Mosunetuzumab Treatment Group Experimental Treatment 1 Intervention

Participants in this group will receive Mosunetuzumab for eight (8) 21-day cycles. Total participation is about 3.5 years.

Mosunetuzumab is already approved in European Union, United States for the following indications:

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Izidore Lossos, MD

Lead Sponsor

Trials

2

Recruited

60+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Mosunetuzumab, the first bispecific antibody approved for lymphoma, shows significant efficacy in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60%.

The approval of mosunetuzumab was based on a phase 2 trial involving patients who had undergone at least two prior lines of systemic therapy, highlighting its potential as a new treatment option for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Cao, Y., Marcucci, EC., Budde, LE.[2023]

In a Phase I study involving 23 Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, mosunetuzumab was found to be well tolerated, with no deaths reported and manageable side effects, primarily neutropenia and cytokine release syndrome.

The treatment showed promising antitumor activity, with 2 patients achieving complete responses and 11 achieving partial responses, indicating its potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Munakata, W., Izutsu, K., Mishima, Y., et al.[2023]

Mosunetuzumab, a T-cell-dependent bispecific antibody, is the first approved treatment for relapsed and refractory follicular lymphoma (FL), showing high efficacy and manageable side effects.

The review highlights the evolving treatment landscape for FL, emphasizing the potential of T-cell-redirecting therapies to improve outcomes for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma. Matarasso, S., Assouline, S.[2023]

In a first-in-human trial involving 230 patients with relapsed or refractory B-cell non-Hodgkin lymphomas, mosunetuzumab demonstrated a manageable safety profile with common side effects like neutropenia and cytokine release syndrome, mostly low-grade and occurring primarily in the first treatment cycle.

The treatment showed promising efficacy, with overall response rates of 34.9% for aggressive and 66.2% for indolent B-NHL, and complete response rates of 19.4% and 48.5%, respectively, indicating that mosunetuzumab can induce durable responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. Budde, LE., Assouline, S., Sehn, LH., et al.[2023]

In a phase 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.

The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde, LE., Sehn, LH., Matasar, M., et al.[2022]

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., et al.[2023]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

In a phase 1b/2 trial involving 120 patients with relapsed/refractory aggressive large B cell lymphoma, the combination of mosunetuzumab and polatuzumab vedotin achieved a high overall response rate of 59.2% and a complete response rate of 45.9%, indicating strong efficacy as a second-line therapy.

The treatment demonstrated a favorable safety profile, with the most common serious side effects being neutropenia (25%) and fatigue (6.7%), and only 16.7% of patients experiencing any-grade cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Budde, LE., Olszewski, AJ., Assouline, S., et al.[2023]

Citations

1. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)02460-7/fulltext

IBCL-1494: MorningSun: Open-Label Phase 2 Trial of the ... Overall response rate (ORR) was 77.8%, with complete metabolic response (CMR) in 63.9% and partial metabolic response in 14%. Median time to response was 2.8 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025024607

MorningSun: Open-Label Phase 2 Trial of the Efficacy and ... Fixed-duration, outpatient SC mosunetuzumab demonstrates robust efficacy, with clinically meaningful (ORR, 77.8%; CMR, 63.9%) durable responses and a manageable ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11210942/

Durable Responses With Mosunetuzumab in Relapsed ... In patients with iNHL or aNHL and a partial response (PR), the median DoR was 7.8 months (95% CI, 4.3 to 8.7) and 3.3 months (95% CI, 2.6 to 4.6) ...

4. bloodcancerstoday.com bloodcancerstoday.com/post/clinically-meaningful-and-durable-response-of-mosunetuzumab-in-mzl

Clinically Meaningful and Durable Response of ... Frontline mosunetuzumab achieved high response rates and sustained remissions in untreated MZL, with manageable CRS and safety in Phase II ...

5. healio.com healio.com/news/hematology-oncology/20250917/video-subcutaneous-mosunetuzumab-demonstrates-efficacy-in-marginal-zone-lymphoma

VIDEO: Subcutaneous mosunetuzumab demonstrates ... The overall response rate was 77.8% and complete metabolic response occurred in 63.9% of patients.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02329

Durable Responses With Mosunetuzumab in Relapsed ... Our study reports the longest follow-up using bispecific antibodies in patients with B-cell non-Hodgkin lymphoma and demonstrates that mosunetuzumab can ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06563505

NCT06563505 | A Phase 2 Trial of Mosunetuzumab and ... Primary Objectives: To determine the safety and efficacy of mosunetuzumab in combination with zanubrutinib as determined by best complete response (CR) rate ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10308681/

Mosunetuzumab and lymphoma: latest updates from 2022 ... Here we provided an overview of the latest clinical data on mosunetuzumab in lymphoma presented at the 2022 ASH Annual Meeting (ASH2022).