Mosunetuzumab + Zanubrutinib for Lymphoma

Overseen By Dai Chihara, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: CNS lymphoma, HIV, Hepatitis B, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, mosunetuzumab (Lunsumio) and zanubrutinib (Brukinsa), to evaluate their effectiveness for people with marginal zone lymphoma that has recurred or not responded to treatment. The goal is to determine if this drug duo is safe and effective for those who have already tried at least one treatment and still need more help. Individuals diagnosed with marginal zone lymphoma who have tried other treatments but continue to experience significant symptoms or tumor growth may be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A inhibitors at least 7 days before starting the study drugs. If you are on corticosteroids, you must be on a dose equivalent to less than 10 mg/day of prednisone for the last 4 weeks. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

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

Research has shown that mosunetuzumab, when used alone, leads to high response rates and lasting remissions, with manageable safety and no long-term issues. Patients tolerated it well over a three-year follow-up period.

The FDA has already approved zanubrutinib for other uses, indicating that its safety is well understood.

Currently, researchers are studying the combination of mosunetuzumab and zanubrutinib. This study is in an early phase, meaning the treatment is still being tested for safety and effectiveness in people. However, previous data on each drug alone provides some reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mosunetuzumab and Zanubrutinib for treating lymphoma because these drugs offer a new approach compared to standard treatments like chemotherapy and radiation. Mosunetuzumab is a bispecific antibody that uniquely targets two different proteins on cancer cells, potentially enhancing the immune system's ability to attack the cancer. Zanubrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, which specifically interferes with pathways essential for the survival of lymphoma cells. Together, this combination targets the cancer from two angles, providing a more precise and potentially more effective treatment option.

What evidence suggests that mosunetuzumab combined with zanubrutinib could be an effective treatment for lymphoma?

Studies have shown that mosunetuzumab can lead to long-lasting improvements and better survival rates in patients with certain types of lymphoma that have returned or are hard to treat. This suggests it might also be effective for marginal zone lymphoma (MZL). Zanubrutinib has demonstrated high success rates in treating other lymphomas, such as mantle cell lymphoma (MCL), with a strong overall response. In this trial, researchers are studying the combination of mosunetuzumab and zanubrutinib to determine if they can improve treatment outcomes for patients with relapsed or hard-to-treat MZL. ^{1 2 4 5 6}

Who Is on the Research Team?

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Marginal Zone Lymphoma (MZL) who have tried other treatments that didn't work or stopped working. Specific eligibility details are not provided, but typically participants need to meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

I can perform daily activities with minimal assistance, more if my condition is lymphoma.

I have at least 3 large tumors that are 3 cm or bigger.

Agree not to share study medication with another person

Exclusion Criteria

I have active brain or spinal cord lymphoma.

I have had cancer other than B-NHL but have been free of it for over 3 years.

I have an autoimmune disease treated with medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab and zanubrutinib for relapsed/refractory marginal zone lymphoma

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Zanubrutinib

Trial Overview The trial is testing the combination of two drugs: Mosunetuzumab and Zanubrutinib, in patients with MZL that has come back after treatment or hasn't responded to previous therapies. It's a Phase 2 trial, which means it focuses on the effectiveness and safety of this drug combo.

How Is the Trial Designed?

Group I: Treatment w/Mosunetuzumab + Zanubrutinib 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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 a first-in-human trial involving 230 patients with relapsed or refractory B-cell non-Hodgkin lymphomas, mosunetuzumab demonstrated a manageable safety profile with common side effects like neutropenia and cytokine release syndrome, mostly low-grade and occurring primarily in the first treatment cycle.

The treatment showed promising efficacy, with overall response rates of 34.9% for aggressive and 66.2% for indolent B-NHL, and complete response rates of 19.4% and 48.5%, respectively, indicating that mosunetuzumab can induce durable responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. Budde, LE., Assouline, S., Sehn, LH., et al.[2023]

In a phase 3 study involving 590 patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating a strong efficacy advantage.

Zanubrutinib demonstrated an acceptable safety profile, with fewer severe adverse events like neutropenia compared to bendamustine-rituximab, suggesting it could be a promising new treatment option for patients with CLL and SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Tam, CS., Brown, JR., Kahl, BS., 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]

In a phase II study involving 217 patients with relapsed/refractory follicular lymphoma, the combination of zanubrutinib and obinutuzumab (ZO) showed a significantly higher overall response rate (ORR) of 69% compared to 46% for obinutuzumab alone, indicating greater efficacy.

The safety profile of ZO was manageable, with common side effects including thrombocytopenia and neutropenia, and serious adverse events like atrial fibrillation occurring in only 3% of patients, suggesting that ZO could be a promising treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma. Zinzani, PL., Mayer, J., Flowers, CR., et al.[2023]

Zanubrutinib demonstrated a high overall response rate of 95.4% in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, with treatment-naïve patients showing even better outcomes (100% response) compared to those with relapsed/refractory disease (91.0%).

The long-term follow-up indicated that earlier treatment with zanubrutinib leads to significantly longer progression-free and overall survival, while maintaining a favorable safety profile, with serious adverse events primarily being infections and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Xu, W., Yang, S., Tam, CS., et al.[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]

In the phase 3 SEQUOIA trial involving adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to the standard treatment of bendamustine plus rituximab (BR).

Patients treated with zanubrutinib reported better health-related quality-of-life outcomes at 12 and 24 weeks, including improvements in global health status, physical functioning, and reduced symptoms of diarrhea, fatigue, and nausea/vomiting compared to those receiving BR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. Ghia, P., Barnes, G., Yang, K., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, was found to be generally well tolerated when combined with obinutuzumab in a phase 1 study involving 81 patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

The combination therapy showed high efficacy, achieving a 100% overall response rate in treatment-naïve CLL patients and a 92% response rate in relapsed/refractory CLL patients, with a 72% response rate in relapsed/refractory FL patients over a median follow-up of 20 to 29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Tam, CS., Quach, H., Nicol, A., et al.[2021]

Citations

1. 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 ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06965

Mosunetuzumab and Zanubrutinib for the Treatment of ... This phase II trial tests the safety, side effects and effectiveness of mosunetuzumab and zanubrutinib in treating patients with marginal zone lymphoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06563505

NCT06563505 | A Phase 2 Trial of Mosunetuzumab and ... Primary Objectives: To determine the safety and efficacy of mosunetuzumab in combination with zanubrutinib as determined by best complete response (CR) rate ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11863491/

Long-term 3-year follow-up of mosunetuzumab in relapsed ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

5. everyone.org everyone.org/explore/compare?id1=543&id2=548

Brukinsa (zanubrutinib) vs Lunsumio (mosunetuzumab- ... In clinical trials, zanubrutinib has demonstrated high response rates in patients with relapsed or refractory MCL. The overall response rate (ORR) in these ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0243.html

A phase 2 trial of mosunetuzumab and zanubrutinib for ... To assess the efficacy and safety of mosunetuzumab combined with zanubrutinib in patients with relapsed or refractory MZL.