Mosunetuzumab for Aggressive B-Cell Lymphoma

Overseen By Armin Ghobadi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Chemotherapy-resistant lymphoma, CNS disease, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 17 cycles (approximately 1 year)

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 1 pilot study examines the feasibility and safety of mosunetuzumab after autologous stem cell transplant for patients with aggressive B cell lymphomas. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain immunosuppressive medications like prednisone over 20 mg within 2 weeks before starting the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Mosunetuzumab for treating aggressive B-cell lymphoma?

Mosunetuzumab has shown promising results in treating relapsed or refractory follicular lymphoma, with an 80% overall response rate and a 60% complete response rate in a phase 2 trial. This suggests it could be effective for other types of B-cell lymphomas as well. ^{1 2 3 4 5}

Is Mosunetuzumab safe for humans?

Mosunetuzumab has been studied in various trials and 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 low level of white blood cells), but these are often mild or moderate. Serious side effects are less common, but they can occur, so it's important to discuss potential risks with your doctor. ^{1 3 6 7 8}

How is the drug mosunetuzumab different from other treatments for aggressive B-cell lymphoma?

Mosunetuzumab is unique because it is a bispecific antibody that targets both CD20 and CD3, redirecting T cells to attack and eliminate cancerous B cells. This 'off-the-shelf' treatment offers a new option for patients with relapsed or refractory B-cell lymphomas, showing high effectiveness with manageable side effects. ^{1 2 3 4 5}

Research Team

Armin Ghobadi, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with aggressive B cell lymphomas who are planning to undergo autologous stem cell transplant. They must have adequate organ function, no recent major infections or vaccinations, and not be pregnant. Men and women must agree to use effective contraception during the study and for 3 months after the last dose of mosunetuzumab.

Inclusion Criteria

My blood counts meet the required levels without recent medical help.

I have been diagnosed with a specific type of aggressive lymphoma.

My lymphoma has spread to my bone marrow, but I meet specific health criteria.

Exclusion Criteria

I don't have any other cancer that could interfere with this study.

I have had progressive multifocal leukoencephalopathy in the past.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Mosunetuzumab is administered in a step-up dosing schedule beginning on Day 49 after autoSCT, with cycles every 21 days

Up to 17 cycles (approximately 1 year)

Visits on C1D1, C1D8, C1D15, and Day 1 of all subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PET-CT restaging around Day 100 post-autoSCT

30 days after last dose of mosunetuzumab

Long-term follow-up

Overall survival and progression-free survival are assessed at 2 years post-autoSCT

2 years and 7 weeks

Treatment Details

Interventions

• Mosunetuzumab

Trial Overview The trial is testing mosunetuzumab as a consolidation therapy post-autologous stem cell transplant in patients with relapsed or refractory aggressive B cell lymphomas. Mosunetuzumab is an engineered antibody designed to direct T cells to kill cancerous B cells.

Participant Groups

Group I: Consolidation Mosunetuzumab Experimental Treatment 1 Intervention

Mosunetuzumab will be given in a step-up dosing schedule beginning on Day 49 after autoSCT on C1D1, C1D8, C1D15, and then Day 1 of all cycles thereafter (each cycle is 21 days). Patients will undergo PET-CT restaging on Day 100 after autoSCT. Those in complete response (CR) will continue mosunetuzumab from Cycle 3 Day 1 through Cycle 8 Day 1 administered at 30 mg IV. Patients not in CR at Day 100 PET-CT will discontinue study treatment.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

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]

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]

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 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 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]

References

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

Mosunetuzumab: First Approval. [2022]

2. 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]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. 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]

8. 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]