Mosunetuzumab for Follicular Lymphoma

Recruiting at 10 trial locations

Overseen By Gilles Salles, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Antiepileptics, others

Disqualifiers: CNS disease, Cardiovascular disease, 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: Up to 1 year

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called mosunetuzumab (also known as Lunsumio) for individuals with follicular lymphoma, a type of blood cancer, who have not yet received any treatment. The study aims to determine the effectiveness of mosunetuzumab alone or in combination with another drug, zanubrutinib. Suitable participants may experience symptoms such as unexplained fevers, night sweats, or significant weight loss and require a treatment plan. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on strong CYP3A inhibitors or inducers, you may need to stop them for Cohort 2. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that mosunetuzumab is generally well-tolerated by people with B-cell lymphoma. Studies have found that it can lead to high response rates and long-lasting remissions without severe side effects. Most side effects are manageable and short-lived.

For the combination of mosunetuzumab and zanubrutinib, studies also show positive safety results. Zanubrutinib effectively fights lymphoma, especially when combined with other treatments. Patients have responded well to this combination, with no major safety concerns reported.

Overall, past research suggests both treatments are safe and manageable for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mosunetuzumab for follicular lymphoma because, unlike standard chemotherapy or monoclonal antibodies like rituximab, it’s a bispecific antibody. This means Mosunetuzumab is designed to engage both cancer cells and T-cells, the immune system's natural fighters, bringing them closer together to enhance the immune response against the tumor. Moreover, the combination of Mosunetuzumab with Zanubrutinib, a Bruton’s tyrosine kinase inhibitor, is an innovative approach that could offer a more targeted and potentially less toxic treatment option. These features make Mosunetuzumab a promising candidate that could improve outcomes for patients with newly diagnosed follicular lymphoma.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that mosunetuzumab, which participants in this trial may receive as a single agent, yields promising results for treating follicular lymphoma, especially in patients who have already undergone other treatments. In earlier studies, about 80% of patients responded to mosunetuzumab, with 60% showing no signs of cancer afterward. Many of these patients remained cancer-free for up to 18 months. Another treatment arm in this trial will evaluate the combination of mosunetuzumab with zanubrutinib, another cancer drug, with hopes for even better results, although specific data on this combination is still being gathered. Overall, mosunetuzumab appears to be a strong option for managing follicular lymphoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Lorenzo Falchi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with newly diagnosed, untreated Follicular Lymphoma (FL) grades 1, 2, or 3A are eligible for this trial. They must have measurable disease and be fit for chemoimmunotherapy. Key requirements include good liver and bone marrow function, no severe heart or lung conditions, no active infections or other cancers within the last two years. Participants need to agree to biopsies and use effective contraception if of childbearing potential.

Inclusion Criteria

Agreement to contraceptive methods for men

My liver is working well.

I need treatment that affects my whole body.

Exclusion Criteria

I have had a solid organ transplant.

Serologic test results indicating HIV infection

Pregnancy, lactation, or intention to become pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab alone or with zanubrutinib for the treatment of newly diagnosed follicular lymphoma

Up to 1 year

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's effectiveness in treating Follicular Lymphoma that hasn't been treated before. It aims to determine whether this drug can help patients with FL by assessing its impact on their cancer.

How Is the Trial Designed?

Group I: Single Agent Mosunetuzumab Experimental Treatment 1 Intervention

Participants with newly diagnosed FL in need of systemic therapy

Group II: Mosunetuzumab + Zanubrutinib Experimental Treatment 2 Interventions

Participants with newly diagnosed FL in need of systemic therapy

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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 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 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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05389293

NCT05389293 | A Study of Mosunetuzumab Alone or With ... The purpose of this study is to find out if mosunetuzumab is an effective treatment in people with follicular lymphoma that was recently diagnosed and have not ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04729

Mosunetuzumab Alone or with Zanubrutinib for the ... This phase II trial tests how well mosunetuzumab with or without zanubrutinib works in treating patients with newly diagnosed follicular lymphoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11863491/

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

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124064000

Mosunetuzumab is Cost-Effective Compared with ... This study found that mosunetuzumab is a cost-effective treatment vs alternative novel treatment options, for adult patients with 3L+ R/R FL.

6. lunsumio-hcp.com lunsumio-hcp.com/

LUNSUMIO™ (mosunetuzumab-axgb) for third-line or later ... Learn how LUNSUMIO™ (mosunetuzumab-axgb) is thought to work and about its safety, administration and side effects for third-line or later follicular ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35803286/

Safety and efficacy of mosunetuzumab, a bispecific ... In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf

LUNSUMIO (mosunetuzumab-axgb) - accessdata.fda.gov The safety and efficacy of LUNSUMIO have not been established in pediatric patients. 8.5 Geriatric Use. Among the 90 patients with relapsed or refractory ...

9. 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.