Mosunetuzumab + Lenalidomide for Follicular Lymphoma

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab (Mosun) + lenalidomide (Len) (Mosun + Len) in participants with follicular lymphoma (FL). This study will also compare the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of IV mosunetuzumab + len vs subcutaneous (SC) mosunetuzumab + len.

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.

What data supports the effectiveness of the drugs Mosunetuzumab and Lenalidomide for treating follicular lymphoma?

Lenalidomide, when combined with rituximab, has been shown to significantly extend the time patients live without their disease getting worse in follicular lymphoma, according to the AUGMENT trial. Mosunetuzumab, a new type of drug that helps the immune system target cancer cells, has been conditionally approved in the EU for patients with follicular lymphoma who have tried other treatments without success. ^{1 2 3 4 5}

How is the drug combination of Mosunetuzumab and Lenalidomide unique for treating follicular lymphoma?

The combination of Mosunetuzumab and Lenalidomide is unique because Mosunetuzumab is a T-cell-engaging bispecific antibody that targets CD20 and CD3, offering a novel mechanism by redirecting T-cells to attack cancer cells, while Lenalidomide is an immunomodulatory drug that enhances the immune response. This combination provides a chemotherapy-free option that could be more effective for patients with relapsed or refractory follicular lymphoma. ^{1 2 3 4 6}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]

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

Mosunetuzumab: First Approval. [2022]

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

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

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

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

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

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy. [2021]

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

Lenalidomide in follicular lymphoma. [2021]