Low Dose Mosunetuzumab for Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Ajay K. Gopal

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Washington

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe allergies, Active infections, Autoimmune, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests the safety, side effects and effectiveness of mosunetuzumab in treating patients with slow growing (indolent) B-cell lymphoma. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.

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.

What data supports the effectiveness of the drug Mosunetuzumab for lymphoma?

Mosunetuzumab has shown promising results in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60% in a phase 2 trial. Additionally, in combination with another drug, it demonstrated durable responses in aggressive large B cell lymphoma, making it a potential option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is low dose Mosunetuzumab safe for humans?

Mosunetuzumab has been studied in patients with different types of lymphoma, and it generally shows a manageable safety profile. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neutropenia (a temporary drop in white blood cells), but these are usually mild to moderate. Serious side effects are rare, but they can occur. ^{1 6 7 8 9}

How is the drug Mosunetuzumab unique for treating lymphoma?

Mosunetuzumab is unique because it is a bispecific antibody that targets both CD20 on B cells and CD3 on T cells, effectively redirecting the body's own immune system to attack lymphoma cells. This 'off-the-shelf' treatment offers a new option for patients with relapsed or refractory follicular lymphoma, especially after other therapies have failed. ^{1 2 3 4 6}

Research Team

Ajay K. Gopal

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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.

Specific laboratory values within defined ranges

Exclusion Criteria

Positive test results for chronic hepatitis B infection

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

I am currently receiving treatment for an autoimmune disease.

Trial Timeline

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

Treatment Details

Interventions

• Mosunetuzumab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

Findings from Research

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]

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]

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 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]

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 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]

5. United States 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. [2023]

7. England 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. [2022]

8. England 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. [2023]

9. United States 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. [2023]