Mosunetuzumab + Lenalidomide for Lymphoma

Recruiting at 2 trial locations

Overseen By BrUOG

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brown University

Must not be taking: Immunosuppressants, Anti-CD20, others

Disqualifiers: Autoimmune disease, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

52 Participants Needed

Trial Summary

What is the purpose of this trial?

BrUOG-401 is a prospective, single-arm, phase 2 trial of first-line therapy in adult patients with previously untreated FL or MZL. All patients will be assigned the same initial treatment plan, modified by interim response assessment (IRA) after Cycle 4. All patients will start treatment with four 21-day cycles (C1-4) of mosunetuzumab alone (using step-up dosing during C1), followed by IRA. Patients who achieve CR at IRA will continue with additional 4 cycles (C5-8) of mosunetuzumab. Patients who achieve PR at IRA will receive mosunetuzumab with lenalidomide augmentation during C5-8. Primary response assessment (PRA) will occur after C8. Patients who remain in PR at PRA will continue for additional 4 cycles (extended augmentation).

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic immunosuppressive medications, except for low-dose corticosteroids, before starting the trial.

What data supports the effectiveness of the drug combination Mosunetuzumab and Lenalidomide for treating lymphoma?

Lenalidomide has shown significant effectiveness in treating various types of B-cell non-Hodgkin lymphoma, both as a single drug and in combination with other treatments, like monoclonal antibodies. It has been particularly effective in relapsed or refractory cases, suggesting potential benefits when combined with other drugs like Mosunetuzumab for lymphoma treatment. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Lenalidomide safe for humans?

Mosunetuzumab and Lenalidomide have been studied separately and in combination with other drugs for lymphoma, showing a generally favorable safety profile. Common side effects include neutropenia (low white blood cell count), fatigue, and cytokine release syndrome (a reaction that can cause fever and low blood pressure), but these are often manageable. Both drugs have been used safely in various lymphoma treatments, suggesting they are generally safe for humans. ^{3 6 7 8 9}

How is the drug Mosunetuzumab + Lenalidomide unique for treating lymphoma?

Mosunetuzumab is a novel drug that engages T-cells to target and destroy cancer cells, making it a potent option for relapsed or refractory follicular lymphoma. When combined with lenalidomide, an oral drug that modifies the immune system, this treatment offers a unique approach by enhancing the immune response against lymphoma cells, providing an 'off-the-shelf' option with manageable side effects. ^{1 3 4 6 10}

Research Team

Adam J Olszewski, MD

Principal Investigator

Brown University

Eligibility Criteria

Adults over 18 with untreated Follicular Lymphoma or Marginal Zone Lymphoma, who can provide tissue samples and consent to study procedures. They must have measurable lymphoma lesions, agree to contraception requirements, and enroll in the lenalidomide REMS program. Excluded are those with severe allergies, certain heart conditions, recent major surgery or infections, liver disease, pregnancy/breastfeeding status, other cancers affecting compliance or results.

Inclusion Criteria

My blood counts meet the required levels, not due to lymphoma.

My tumor is causing symptoms or affecting how my organs work.

Glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula.

Exclusion Criteria

I have no cancer history that could interfere with this study, or if I do, it's been in remission for over 2 years.

I have severe heart issues, including recent heart attack or unstable heart rhythm.

I do not have active infections or certain viral conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab alone for four 21-day cycles, followed by interim response assessment. Depending on response, treatment continues with mosunetuzumab alone or with lenalidomide augmentation for additional cycles.

24 weeks

Primary Response Assessment

Primary response assessment occurs after Cycle 8 to evaluate complete response rate.

1 week

Extended Augmentation

Participants who remain in partial response at primary response assessment continue for additional 4 cycles with extended augmentation.

12 weeks

Follow-up

Participants are monitored for progression-free survival and other outcomes.

Approximately 5 years

Treatment Details

Interventions

• Lenalidomide
• Mosunetuzumab

Trial Overview The trial tests mosunetuzumab alone for four cycles followed by an interim response assessment (IRA). Depending on IRA results (complete response or partial response), patients may continue with mosunetuzumab alone or receive it augmented with lenalidomide for another four cycles. The primary response is assessed after eight cycles.

Participant Groups

Group I: Planned Therapy Experimental Treatment 2 Interventions

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?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Adam Olszewski

Lead Sponsor

Trials

3

Recruited

80+

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

Lenalidomide is an effective oral immunomodulator approved for treating relapsed/refractory mantle cell lymphoma (MCL) after two prior therapies, showing significant activity in various B-cell non-Hodgkin lymphomas (NHL).

Combining lenalidomide with rituximab (R2) has demonstrated promising results in both first-line and relapsed/refractory settings, and ongoing trials are evaluating its use in combination with immunochemotherapy regimens like R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Witzig, TE., Nowakowski, GS., Habermann, TM., et al.[2020]

In a study of 33 patients with relapsed/refractory non-Hodgkin lymphoma, the GROC-Rev chemotherapy regimen followed by lenalidomide maintenance therapy resulted in a 61% overall response rate, with 39% achieving complete response (CR).

The treatment was generally well-tolerated, although some patients experienced significant adverse events like neutropenia and infections, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). Cabanillas, F., Rivera, N., Acosta, M., et al.[2022]

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

In a phase 2 study involving 89 patients with relapsed or refractory follicular lymphoma, 79% achieved an overall response after treatment with lenalidomide and obinutuzumab, demonstrating significant efficacy in this patient population.

The treatment had a manageable safety profile, with common adverse events including neutropenia and asthenia, and serious adverse events reported in 34% of patients, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Morschhauser, F., Le Gouill, S., Feugier, P., et al.[2019]

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]

The combination of oral lenalidomide and obinutuzumab was found to be well tolerated and effective in treating relapsed or refractory follicular lymphoma, with a response rate of 63.2% among participants.

The study established a recommended dose of lenalidomide at 20 mg, as higher doses increased the risk of grade 3/4 neutropenia, although no maximum tolerated dose was reached during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. Morschhauser, F., Salles, G., Le Gouill, S., et al.[2021]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. [2020]

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

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). [2022]

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

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

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

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]

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

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. [2019]

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

Mosunetuzumab: First Approval. [2022]

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

An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. [2021]

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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

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