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

Recruiting at 61 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

188 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Mosunetuzumab +/- Polatuzumab Vedotin for Diffuse Large B-Cell Lymphoma?

Research shows that the combination of mosunetuzumab and polatuzumab vedotin has a favorable safety profile and leads to durable responses in patients with relapsed or refractory large B-cell lymphoma, with a 59.2% overall response rate and a 45.9% complete response rate. Additionally, polatuzumab vedotin has been effective in other studies, showing a 40% complete response rate when combined with other treatments for similar conditions. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Polatuzumab Vedotin safe for humans?

The combination of Mosunetuzumab and Polatuzumab Vedotin has shown a favorable safety profile in clinical trials for relapsed or refractory large B-cell lymphoma, with common side effects including neutropenia (low white blood cell count) and fatigue. Any-grade cytokine release syndrome (a reaction that can cause fever and flu-like symptoms) occurred in 16.7% of patients. ^{1 4 5 6 7}

How is the drug Mosunetuzumab different from other treatments for diffuse large B-cell lymphoma?

Mosunetuzumab is unique because it is a bispecific antibody that engages both CD20 on B-cells and CD3 on T-cells, helping the immune system target and destroy cancer cells. When combined with Polatuzumab Vedotin, which targets CD79b on B-cells, it offers a novel approach for treating relapsed or refractory diffuse large B-cell lymphoma, especially for patients who are not eligible for transplant. ^{1 4 5 6 8}

What is the purpose of this trial?

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. 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]

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

Outcome of relapsed/refractory diffuse large B-cell lymphoma patients treated with polatuzumab vedotin-based therapy: real-life experience. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. England 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. [2023]

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

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]

6. New Zealand 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. [2022]

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

Cell-of-Origin Effect of Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma: No Ordinary Subgroup Analysis. [2023]

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

Mosunetuzumab: First Approval. [2022]