Mosunetuzumab + Lenalidomide for Follicular Lymphoma

Recruiting at 34 trial locations

Overseen By Reference Study ID Number: CO41942 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Thalidomide

Disqualifiers: CNS lymphoma, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: approximately 36 weeks

237 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, mosunetuzumab (Lunsumio) and lenalidomide (Revlimid), for individuals with follicular lymphoma, a type of blood cancer. Researchers aim to assess the safety and effectiveness of these treatments and determine if injecting the treatment under the skin is as effective as administering it through an IV. The trial seeks participants with follicular lymphoma that hasn't responded well to previous treatments and who require further therapy. For those who have struggled with other lymphoma treatments and need new options, this trial might be suitable. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering a chance to explore new treatment possibilities.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have taken certain immunosuppressive medications within 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining mosunetuzumab with lenalidomide is generally safe for patients. In studies involving patients whose previous treatments failed, this combination yielded promising results. Most side effects were mild and manageable.

For the under-the-skin version of mosunetuzumab, early results indicate it can be safely administered in an outpatient setting. Some cases of cytokine release syndrome (CRS) occurred, but the rates were manageable.

The version given intravenously also demonstrated manageable safety. Whether used alone or with lenalidomide, it proved effective and generally well-tolerated.

In summary, both forms of mosunetuzumab with lenalidomide have been tested and found to be generally safe, with manageable side effects, making them a promising option for further study in treating follicular lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mosunetuzumab combined with lenalidomide for treating follicular lymphoma because of its innovative dual-action mechanism. Unlike traditional treatments like rituximab, which target CD20 on B-cells, mosunetuzumab is a bispecific antibody that simultaneously binds to CD20 on B-cells and CD3 on T-cells. This unique approach effectively brings cancer-fighting T-cells directly to the tumor, potentially enhancing the immune response. Additionally, the treatment offers flexibility in administration, with both subcutaneous and intravenous options, which could improve patient comfort and adherence.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

In this trial, participants will receive mosunetuzumab either subcutaneously or intravenously, combined with lenalidomide. Studies have shown that mosunetuzumab effectively treats follicular lymphoma, especially when combined with lenalidomide. Research indicates that patients receiving only mosunetuzumab had response rates between 68% and 80%, with many experiencing positive outcomes. Combining mosunetuzumab with lenalidomide appears even more effective, showing higher response rates and good tolerance in patients with recurrent or difficult-to-treat lymphoma. Both administration methods for mosunetuzumab have demonstrated promising safety and disease management results. These findings suggest this combination could be a strong option for people with follicular lymphoma. ^{1 4 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 follicular lymphoma who've had at least one prior treatment. They must be in stable condition, not have severe allergies to monoclonal antibodies or certain infections, and agree to contraception if of childbearing potential. Those with a history of certain other cancers or conditions are excluded.

Inclusion Criteria

My lymphoma shows up on PET scans.

My blood counts are within normal ranges, unless affected by my lymphoma.

I have untreated follicular lymphoma and need systemic therapy as per GELF criteria.

Exclusion Criteria

I have a significant history of liver problems.

Pregnant or lactating or intending to become pregnant during the study

You have a history of using illegal drugs or abusing alcohol in the past year, according to the doctor's assessment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab plus lenalidomide for 12 cycles (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

approximately 36 weeks

Maintenance

Participants with complete or partial metabolic response receive maintenance therapy with SC mosunetuzumab every 8 weeks for an additional 9 cycles

approximately 72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Mosunetuzumab

Trial Overview The study tests the combination of mosunetuzumab (given intravenously or subcutaneously) with lenalidomide in patients with follicular lymphoma. It aims to compare safety, how the body processes the drugs, and their effectiveness against this type of cancer.

How Is the Trial Designed?

Group I: Subcutaneous (SC) Mosunetuzumab + Lenalidomide (Non-randomized) Experimental Treatment 2 Interventions

Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward). Participants that have received complete metabolic response (CMR) or partial metabolic response (PMR) after 12 cycles of induction therapy with mosunetuzumab + lenalidomide will receive maintenance therapy with SC mosunetuzumab every 8 weeks (Q8W) for an additional 9 cycles.

Group II: Intravenous (IV) Mosunetuzumab + Lenalidomide (Non-randomized) Experimental Treatment 3 Interventions

Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Group III: Arm B: SC Mosunetuzumab + Len (Randomized) Experimental Treatment 2 Interventions

Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Group IV: Arm A: IV Mosunetuzumab + Len (Randomized) Experimental Treatment 2 Interventions

Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

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

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 the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

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]

The combination of lenalidomide and rituximab (LR) showed a significantly higher overall response rate (76%) compared to lenalidomide alone (53%) in patients with recurrent follicular lymphoma, indicating that LR is more effective in treating this condition.

Both treatment regimens had similar rates of severe adverse events (grade 3 to 4), but lenalidomide alone resulted in more treatment failures, suggesting that LR may provide a better balance of efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). Leonard, JP., Jung, SH., Johnson, J., et al.[2022]

Lenalidomide is an effective and well-tolerated treatment for multiple myeloma and shows promise for patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma.

The review highlights the potential of lenalidomide, especially in combination with rituximab, as a therapeutic option, aiming to guide future clinical studies to enhance survival rates for these lymphoma types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy. Desai, M., Newberry, KJ., Romaguera, J., et al.[2021]

Lenalidomide, when used in combination with rituximab, has been shown to be an effective treatment for patients with relapsed or refractory follicular lymphoma, offering a chemotherapy-free option.

This combination therapy improves outcomes compared to using rituximab alone and may serve as a viable alternative to traditional chemoimmunotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04246086

NCT04246086 | A Study Evaluating the Safety, ... This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025024516

IBCL-1256: Mosunetuzumab in Relapsed/Refractory ... In mosunetuzumab monotherapy trials, the overall response rates (ORRs) were 80%, 68%, 78.9%, and 74%, and the complete response (CR) rates were 60%, 50%, 68.4%, ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6512/527475/Efficacy-and-Safety-of-Mosunetuzumab-in-Relapsed

Efficacy and Safety of Mosunetuzumab in Relapsed/Refractory ... Mosunetuzumab in combination with lenalidomide demonstrated higher efficacy and good tolerability in patients with relapsed/refractory non-Hodgkin lymphoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430742/

P1125: CELESTIMO: A PHASE III TRIAL EVALUATING ... ASH 2021). Preliminary data from a Phase Ib study have suggested favorable safety and promising activity of M in combination with lenalidomide (Len), a potent ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/605/503686/Preliminary-Findings-of-a-Phase-Ib-II-Trial

Preliminary Findings of a Phase Ib/II Trial Indicate ... A Phase Ib/II trial indicate manageable safety and promising efficacy for Mosunetuzumab in combination with Lenalidomide (M+Len) in previously untreated (1L) ...

6. 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 ... We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/ ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/non-hodgkins-lymphoma/a-study-evaluating-the-safety--pharmacokinetics--and-ef-94381.html

Clinical Trial - Follicular Lymphoma - mosunetuzumab plus... This clinical trial aims to test the safety and effectiveness of mosunetuzumab in combination with lenalidomide and to understand how the body processes the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04712097

NCT04712097 | A Study Evaluating the Efficacy and Safety ... This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with ...