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

Trial Summary

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.

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

Mosunetuzumab has been conditionally approved in the EU for treating relapsed or refractory follicular lymphoma, showing its potential effectiveness. Zanubrutinib, when combined with obinutuzumab, showed a 72% overall response rate in patients with relapsed or refractory follicular lymphoma, indicating it may be effective in similar conditions. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Zanubrutinib safe for humans?

Mosunetuzumab and Zanubrutinib have been studied separately and in combination with other drugs for different types of lymphoma. Mosunetuzumab has shown a manageable safety profile, with common side effects like cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neutropenia (low white blood cell count). Zanubrutinib, when combined with other drugs, was generally well tolerated, with common side effects including infections, fatigue, and low blood cell counts. ^{1 2 4 6 7}

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

The combination of Mosunetuzumab and Zanubrutinib is unique because Mosunetuzumab is a bispecific antibody that helps the immune system target and destroy cancer cells, while Zanubrutinib is a highly selective inhibitor that blocks a protein involved in cancer cell growth. This dual approach may offer a novel way to treat relapsed or refractory lymphoma by combining immune system engagement with targeted cancer cell inhibition. ^{1 2 3 8 9}

What is the purpose of this trial?

To assess the efficacy and safety of mosunetuzumab combined with zanubrutinib in patients with relapsed or refractory MZL.

Research Team

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

My organ and bone marrow functions are within normal ranges.

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

Exclusion Criteria

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

I have active brain or spinal cord lymphoma.

I am on long-term medication that strongly affects liver enzymes.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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 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]

References

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

Mosunetuzumab: First Approval. [2022]

2. United States 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. [2023]

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

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. [2021]

5. England 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. [2023]

6. 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]

7. 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]

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

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. [2022]

9. United States 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. [2023]