Mosunetuzumab + Chemotherapy for Diffuse Large B-Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Immunosuppressants, Cannabis

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 4

Duration: 18 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the combination of mosunetuzumab, a type of immunotherapy, with chemotherapy to treat certain aggressive forms of lymphoma, a type of blood cancer. Researchers aim to assess the safety and effectiveness of this treatment combination for patients who have not yet started any other treatments. It targets patients with specific genetic markers (c-Myc rearrangement) in their lymphoma, identifiable through standard medical tests. This trial suits those with high-grade B-cell lymphoma or diffuse large B-cell lymphoma who have not previously received treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that systemic immunosuppressive medications are generally not allowed, except for certain corticosteroids. Herbal therapies for lymphoma and cannabis products are also not permitted during the study.

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

Research has shown that mosunetuzumab, when used alone, is generally well-tolerated by patients with diffuse large B-cell lymphoma, a type of blood cancer. In studies, patients who received this treatment responded well, even after many previous treatments. Serious side effects were rare, making it a promising option for those with difficult-to-treat cancer.

The chemotherapy part of the trial includes drugs such as etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone. Doctors have long used these well-known chemotherapy drugs to treat similar conditions. While they can cause side effects like nausea, tiredness, and hair loss, medical care usually manages these effects.

In summary, both mosunetuzumab and the chemotherapy drugs have a good safety record. They have been used in similar conditions before, providing some assurance about their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mosunetuzumab for treating Diffuse Large B-Cell Lymphoma because it represents a novel approach that could enhance treatment effectiveness. Unlike the standard chemotherapy regimens, Mosunetuzumab is a bispecific antibody that targets CD20 and CD3, which helps the immune system to find and destroy cancer cells more effectively. This dual-targeting mechanism offers a fresh strategy that could potentially increase cancer cell kill rates compared to traditional chemotherapy alone. Additionally, the combination with EPOCH chemotherapy aims to maximize the anti-tumor activity, potentially leading to better outcomes for patients.

What evidence suggests that mosunetuzumab with chemotherapy could be effective for diffuse large B-cell lymphoma?

Research has shown that mosunetuzumab holds promise for treating diffuse large B-cell lymphoma (DLBCL). In this trial, participants will receive a combination of mosunetuzumab and chemotherapy. Previous studies have demonstrated that mosunetuzumab, when used with chemotherapy, was more effective and well-tolerated by most patients. One study found that 24% of patients with relapsed or hard-to-treat DLBCL had a complete response when using mosunetuzumab alone. Additionally, combining mosunetuzumab with another drug reduced the risk of disease progression or death by 59% in a different treatment setting. These findings suggest that mosunetuzumab, especially when combined with chemotherapy, could effectively treat DLBCL. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen E. Spurgeon

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with untreated high grade B cell lymphoma or diffuse large B cell lymphoma that tests positive for c-Myc rearrangement. Participants should not have had previous treatments and must be suitable for immunotherapy and chemotherapy.

Inclusion Criteria

Participant must be able to comply with the study protocol and procedures

I have at least one measurable cancerous lesion.

My cancer is at least Stage II and has a moderate to high risk score.

Exclusion Criteria

Specific coagulation abnormalities

I am using herbal therapies for my lymphoma.

I use cannabis products.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive mosunetuzumab and DA EPOCH chemotherapy in cycles of 21 days for up to 6 cycles

18 weeks

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Mosunetuzumab

Trial Overview The trial is testing mosunetuzumab, a monoclonal antibody, combined with chemotherapy drugs (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone) to see if they're safe and effective against certain types of B cell lymphoma.

How Is the Trial Designed?

Group I: Treatment (Mosunetuzumab and EPOCH) Experimental Treatment 14 Interventions

Patients receive mosunetuzumab IV, over 2-4 hours, on day 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients receive etoposide IV, doxorubicin IV, and vincristine IV on days 1-4, cyclophosphamide IV, over 2 hours, on day 5 and prednisone PO BID on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles. Patients undergo bone marrow aspiration and biopsy, tumor biopsy and may undergo echocardiography or MUGA at screening and PET scan, CT scan or MRI and blood sample collection throughout the study.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

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

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

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 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, 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37581593/

safety and efficacy results from a phase 2 study Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the ...

2. 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 ... Median progression-free survival was 24.0 months (95% CI, 12.0 to NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) ...

3. roche.com roche.com/media/releases/med-cor-2025-06-20

Roche's Lunsumio and Polivy combination significantly ... The Lunsumio and Polivy combination demonstrated a 59% reduction in risk of disease progression or death compared to R-GemOx.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19013

Efficacy and safety of mosunetuzumab-based regimens as ... Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to ...

5. ashpublications.org ashpublications.org/bloodadvances/article/7/17/4926/495381/Mosunetuzumab-monotherapy-is-active-and-tolerable

Mosunetuzumab monotherapy is active and tolerable in ... Mosunetuzumab is active as a single agent and yields CRs in 24% of heavily pretreated patients with R/R DLBCL.

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

Mosunetuzumab Safety Profile in Patients With Relapsed ... We present interim safety data from the mosunetuzumab GO29781 (NCT02500407) phase I/II dose-escalation study in R/R non-Hodgkin lymphoma (NHL), focusing on FL.