Low Dose Mosunetuzumab for Lymphoma

Overseen By Ajay Gopal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe allergies, Active infections, Autoimmune, 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: 4

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of mosunetuzumab for individuals with slow-growing B-cell lymphoma. Mosunetuzumab is a medicine designed to stop cancer cells from growing and spreading. The trial seeks participants diagnosed with indolent B-cell non-Hodgkin lymphoma, such as follicular or marginal zone lymphoma, who have not yet received treatment. Participants should have a low tumor burden and no severe symptoms affecting daily life. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, ongoing systemic corticosteroid treatment is not allowed, except for non-tumor and non-immunosuppressive uses up to a maximum of 10 mg/day of prednisone or equivalent.

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

Research has shown that mosunetuzumab is generally well-tolerated by patients with relapsed or refractory non-Hodgkin lymphoma. One study found that about 47% of patients experienced infections after starting treatment, but these were mostly mild, such as common colds. Another study reported that temporary swelling, known as tumor flare, occurred in 4% of patients. Importantly, long-term follow-up indicates that mosunetuzumab does not present major safety concerns over time. Overall, the safety of mosunetuzumab appears manageable, with side effects that are usually not severe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mosunetuzumab is unique because it is a bispecific monoclonal antibody that targets both CD20 on B-cells and CD3 on T-cells. This dual-targeting approach aims to bring T-cells directly to the cancerous B-cells to help the immune system attack the lymphoma more efficiently. Unlike traditional chemotherapy or single-target antibodies, mosunetuzumab offers a more precise mechanism that could potentially lead to fewer side effects and better outcomes. Researchers are particularly excited about its potential to improve the body's natural immune response against lymphoma, providing a new avenue of hope for those who haven’t responded well to existing treatments.

What evidence suggests that mosunetuzumab might be an effective treatment for lymphoma?

Studies have shown that mosunetuzumab, which participants in this trial will receive, can help achieve long-lasting remission in patients with certain types of lymphoma, such as follicular lymphoma, even when other treatments have failed. Specifically, about 60% of patients who responded to this treatment continued to benefit for over 18 months. Research indicates that mosunetuzumab is effective, with positive results enduring over time. Additionally, the treatment is generally safe, with manageable side effects and no major long-term safety concerns reported. ^{1 3 6 7 8}

Who Is on the Research Team?

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with slow-growing B-cell lymphomas, such as Marginal Zone Lymphoma and Follicular Lymphoma. Participants should meet specific health criteria to be eligible.

Inclusion Criteria

I have a type of slow-growing B-cell lymphoma and haven't had treatment yet.

I can understand and sign the consent form.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

Positive test results for chronic hepatitis B infection

I am currently receiving treatment for an autoimmune disease.

I do not have any major health issues that could affect the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, 15, and 22. Patients also undergo blood sample collection and PET/CT on study.

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups at week 13, at 6 months, and then for up to 5 years.

5 years

Multiple visits as per institutional standards

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab

Trial Overview The trial is testing the safety and effectiveness of a monoclonal antibody called Mosunetuzumab in treating indolent B-cell lymphoma. It includes tests like CT scans, MRIs, PET scans, and biospecimen collection.

How Is the Trial Designed?

Group I: Treatment (mosunetuzumab) Experimental Treatment 6 Interventions

Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, 15 and 22. Patients also undergo blood sample collection and PET/CT on study. Patients may undergo CT and/or MRI as clinically indicated and may undergo collection of oral and/or rectal swabs on study.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

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]

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 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]

In a phase 2 study involving 40 patients with untreated diffuse large B-cell lymphoma (DLBCL), the combination of mosunetuzumab and CHOP chemotherapy showed high efficacy, with objective and complete response rates of 87.5% and 85.0%, respectively.

The safety profile of mosunetuzumab was manageable, with most adverse events being mild (grade 1 or 2), and only 2.5% of patients experiencing severe neurological side effects, indicating that this treatment could be a promising option for patients with DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Olszewski, AJ., Phillips, TJ., Hoffmann, MS., 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, 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 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]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/7/708/525779/Long-term-3-year-follow-up-of-mosunetuzumab-in

Long-term 3-year follow-up of mosunetuzumab in relapsed or ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

2. lunsumio.com lunsumio.com/results/clinical-trial-results.html

Clinical trial results This study was a phase 2 clinical trial, meaning it studied an investigational treatment to test how well it worked and monitored for potential side effects ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41037766/

primary results of the phase 3 SUNMO trial Conclusion: Mosun-Pola demonstrated superior efficacy verus R-GemOx, with significant improvements in both overall response rate and progression ...

4. lunsumio-hcp.com lunsumio-hcp.com/efficacy/clinical-trial-results.html

LUNSUMIO™ (mosunetuzumab-axgb) Efficacy | HCP ~6 out of 10 patients who achieved an overall response maintained response at 18 months. ... 7 out of 10 patients who achieved complete response maintained ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124107719

Long-term 3-year follow-up of mosunetuzumab in relapsed ... With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions and manageable safety with no long-term concerns.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38195322/

Mosunetuzumab Safety Profile in Patients With Relapsed ... Materials and methods: We present interim safety data from the mosunetuzumab GO29781 (NCT02500407) phase I/II dose-escalation study in R/R non-Hodgkin lymphoma ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023021948

Mosunetuzumab Safety Profile in Patients With Relapsed ... In total, 102/218 patients (46.8%) in the R/R NHL cohort experienced 182 infection AEs following initial treatment with mosunetuzumab (most commonly upper ...

8. hematologyadvisor.com hematologyadvisor.com/news/follicular-lymphoma-fixed-duration-mosunetuzumab-durable-response/

Fixed-Duration Subcutaneous Mosunetuzumab Shows ... A phase 1/2 study showed durable remission, manageable safety in pts with R/R follicular lymphoma who received fixed-duration ...