Mosunetuzumab +/- Polatuzumab Vedotin for Diffuse Large B-Cell Lymphoma

No longer recruiting at 71 trial locations

Overseen By Reference Study ID Number: GO40554 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Disqualifiers: Transformed lymphoma, CNS lymphoma, 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: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called mosunetuzumab for people with diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. The study examines the safety and effectiveness of mosunetuzumab, either alone or with another drug, polatuzumab vedotin (an antibody-drug conjugate), for those who haven't received other treatments or didn’t respond well to initial therapy. Participants should have a measurable lymph node or tumor size and should not have had certain previous treatments or health conditions like significant liver disease. This trial may suit those with DLBCL who have had limited or no success with previous treatments or are older and not suited for standard chemotherapy. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

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, if you have had prior treatment for DLBCL with chemotherapy, immunotherapy, or biologic therapy, you may not be eligible for the trial.

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

Research has shown that mosunetuzumab is generally well-tolerated. In studies, patients with relapsed or difficult-to-treat B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), experienced few serious side effects. Some patients reported cytokine release syndrome (CRS), which can cause symptoms like fever and tiredness, but these were uncommon.

When combined with polatuzumab vedotin, mosunetuzumab maintains a good safety profile. This combination suits patients who cannot undergo a transplant, with side effects that most can manage. The treatment has demonstrated lasting benefits, making it a promising option for those needing alternatives to traditional therapies.

Overall, both mosunetuzumab alone and with polatuzumab vedotin have shown manageable safety profiles in previous studies, making them potential options for patients considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy options for Diffuse Large B-Cell Lymphoma (DLBCL), mosunetuzumab works by engaging the body's immune system to specifically target and destroy cancer cells. This is achieved through its unique mechanism of action as a bispecific antibody, which connects T-cells directly to cancer cells. Researchers are particularly excited about the potential of mosunetuzumab for elderly or unfit patients, as it may offer a more tolerable alternative to traditional chemotherapy. Additionally, combining mosunetuzumab with polatuzumab vedotin, which delivers a targeted chemotherapy payload directly to cancer cells, could enhance effectiveness and broaden treatment possibilities for those who cannot undergo more aggressive treatments.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

Studies have shown promising results for mosunetuzumab in treating diffuse large B-cell lymphoma (DLBCL). In this trial, some participants will receive mosunetuzumab alone, which research indicates can lead to complete responses in about 24% of patients unresponsive to other treatments. Other participants will receive a combination of mosunetuzumab and polatuzumab vedotin, which significantly reduced the risk of disease progression or death by 59% compared to some other treatments. These findings suggest that mosunetuzumab, both alone and in combination, could be effective options for patients with DLBCL. This combination helps the body's immune cells attack cancer cells, offering a new way to fight the disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with Diffuse Large B-Cell Lymphoma (DLBCL) who've had certain responses to first-line therapy or are elderly/unfit and untreated. Participants must have adequate organ function, an ECOG status of 0-2 (or improved to ≤2 if initially at 3), measurable lymphoma lesions, and no severe comorbidities. Exclusions include transformed lymphoma, prior transplants, significant liver disease or cardiovascular issues, CNS conditions including lymphoma, recent SARS-CoV-2 infection, history of HLH or PML, active viral infections like hepatitis B/C or HIV.

Inclusion Criteria

I have a tumor that can be measured and is larger than 1.5 cm if it's in a lymph node or larger than 1.0 cm if it's not in a lymph node.

My blood counts are within a healthy range.

I can care for myself and am under 80 if living in South Korea.

Exclusion Criteria

Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1

I have a significant history of liver problems.

My lymphoma has changed into a more aggressive form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab following first-line immunochemotherapy or as monotherapy/combination therapy in elderly/unfit participants

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Polatuzumab Vedotin
• Tocilizumab

Trial Overview The study tests mosunetuzumab as a follow-up treatment after initial chemoimmunotherapy in DLBCL patients with stable disease/partial response. It also examines mosunetuzumab alone or combined with polatuzumab vedotin in elderly/unfit patients without prior treatments. The drug's safety and effectiveness will be assessed through IV and subcutaneous administration methods.

How Is the Trial Designed?

Group I: Elderly/Unfit Previously Untreated Monotherapy (Cohort B) Experimental Treatment 2 Interventions

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).

Group II: Elderly/Unfit Previously Untreated Combination Therapy (Cohort C) Experimental Treatment 3 Interventions

Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.

Group III: Consolidation Therapy (Cohort A) Experimental Treatment 2 Interventions

Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[2022]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, 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 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]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[2023]

The POLARIX trial indicates that polatuzumab vedotin combined with chemotherapy is more effective in treating untreated large B-cell lymphoma, particularly in patients with the activated B-cell subtype.

This finding is supported by both preclinical and clinical evidence, highlighting the importance of the cell-of-origin in determining the efficacy of polatuzumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-of-Origin Effect of Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma: No Ordinary Subgroup Analysis. Russler-Germain, DA., Cliff, ERS., Bartlett, NL.[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. clinicaltrials.gov clinicaltrials.gov/study/NCT06828991

NCT06828991 | A Study to Evaluate the Impact of ... Older patients with diffuse large B- cell lymphoma (DLBCL) do not have the same rates of disease control as younger patients and are at risk for toxicity.

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

Mosunetuzumab Safety Profile in Patients With Relapsed ... Mosunetuzumab monotherapy as treatment for R/R B-cell NHL, including FL, was associated with low rates of severe AEs (including CRS) and is suitable for ...

8. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(21)01896-6/fulltext

Mosunetuzumab (Mosun) Monotherapy for Elderly/Unfit ... Mosun, a full-length, humanized, IgG1 CD20×CD3 bispecific antibody, demonstrated efficacy/safety in relapsed/refractory DLBCL (NCT02500407; Schuster, et al. ASH ...