Mosunetuzumab + Chemotherapy for B-Cell Lymphoma

Overseen By Nancy L. Bartlett

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants

Disqualifiers: CNS disease, Autoimmune disease, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests adding mosunetuzumab to strong chemotherapy for patients with aggressive B cell lymphoma who haven't responded to other treatments. The drug helps the immune system find and kill cancer cells, aiming to improve treatment before a stem cell transplant. Mosunetuzumab has shown promising results in recent trials.

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, you cannot take 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 drug Mosunetuzumab for B-Cell Lymphoma?

Mosunetuzumab has shown promising results in treating relapsed or refractory follicular lymphoma, with an 80% overall response rate and a 60% complete response rate in a phase 2 trial, making it an effective option for patients who have tried other treatments without success. ^{1 2 3 4 5}

Is Mosunetuzumab safe for humans?

Mosunetuzumab has been studied in clinical trials for lymphoma, showing a favorable safety profile. Common side effects include neutropenia (low white blood cell count) and fatigue, with some patients experiencing cytokine release syndrome (a reaction from immune cells). ^{2 3 6 7 8}

What makes the drug mosunetuzumab unique for treating B-cell lymphoma?

Mosunetuzumab is unique because it is a bispecific antibody that targets both CD20 and CD3, redirecting T cells to attack and eliminate cancerous B cells. This approach is different from traditional therapies and offers a new option for patients with relapsed or refractory B-cell lymphomas. ^{1 2 3 6 9}

Research Team

David Russler-Germain, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with certain aggressive B cell lymphomas that have come back or didn't respond to initial treatments. They should be planning an autologous stem cell transplant and must not have had more than two prior chemotherapy lines. Participants need normal blood counts, no major recent surgeries, and can't be pregnant or breastfeeding. Those with autoimmune diseases, a history of severe allergies to monoclonal antibodies, active infections, or liver disease are excluded.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I am 18 years old or older.

Normal laboratory values

Exclusion Criteria

My lymphoma has affected my central nervous system.

I do not have any other cancer that could interfere with this study.

I haven't had CAR-T cell therapy in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab in combination with platinum-based salvage chemotherapy for 4 cycles (each cycle is 21 days)

12 weeks

4 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

48 months

Treatment Details

Interventions

• DHAX (Alkylating agents)
• ICE (Alkylating agents)
• Mosunetuzumab (Monoclonal Antibodies)

Trial Overview The study tests mosunetuzumab combined with platinum-based salvage chemotherapy (DHAX or ICE) in patients aiming for stem cell transplantation. It's designed to see if this combination is safe and potentially better than current chemoimmunotherapy options that use rituximab retreatment.

Participant Groups

Group I: Arm B: Mosunetuzumab + ICE Experimental Treatment 2 Interventions

* 4 cycles (cycle=21 days) of mosunetuzumab with ICE salvage chemotherapy (selected at the discretion of the treating physician). * For patients tolerating Cycle 1 with step-up of treatment, Cycles 2 and beyond will consist of mosunetuzumab administered as a single dose on Day 1 along with ICE. Patients will undergo PET-CT restaging prior to Cycle 3. Patients with SD or PD based on restaging after Cycle 2 will discontinue study treatment; further treatment will be administered at the discretion of the treating physician. Patients responding to study treatment based on restaging after Cycle 2 may receive up to two additional cycles of study treatment before consolidation therapy (e.g., autologous stem cell transplantation, chimeric antigen receptor T-cell therapy) at the discretion of the treating physician.

Group II: Arm A: Mosunetuzumab + DHAX Experimental Treatment 2 Interventions

* 4 cycles (cycle=21 days) of mosunetuzumab with DHAX salvage chemotherapy (selected at the discretion of the treating physician). * For patients tolerating Cycle 1 with step-up of treatment, Cycles 2 and beyond will consist of mosunetuzumab administered as a single dose on Day 1 along with DHAX. Patients will undergo PET-CT restaging prior to Cycle 3. Patients with SD or PD based on restaging after Cycle 2 will discontinue study treatment; further treatment will be administered at the discretion of the treating physician. Patients responding to study treatment based on restaging after Cycle 2 may receive up to two additional cycles of study treatment before consolidation therapy (e.g., autologous stem cell transplantation, chimeric antigen receptor T-cell therapy) at the discretion of the treating physician.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

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]

Mosunetuzumab, the first bispecific antibody approved for lymphoma, shows significant efficacy in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60%.

The approval of mosunetuzumab was based on a phase 2 trial involving patients who had undergone at least two prior lines of systemic therapy, highlighting its potential as a new treatment option for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Cao, Y., Marcucci, EC., Budde, LE.[2023]

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]

Galiximab, a monoclonal antibody targeting CD80, was safely combined with rituximab in a study of 73 patients with relapsed or refractory follicular non-Hodgkin's lymphoma, showing a well-tolerated profile with common side effects like lymphopenia and fatigue.

The combination therapy resulted in a 66% overall response rate at the recommended dose of galiximab, with a median progression-free survival of 12.1 months, suggesting it may effectively delay the need for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma. Leonard, JP., Friedberg, JW., Younes, A., et al.[2020]

In a study of 7 patients with primary cutaneous B-cell lymphoma who had relapsed after chemotherapy, the combination of intravenous rituximab and single-dose cyclophosphamide resulted in an impressive overall response rate of 85.7%, with 5 patients achieving complete remission.

The treatment was well tolerated, and after a median follow-up of 13 months, most patients remained disease-free for significant durations, indicating promising efficacy and safety for this approach in managing relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. Fierro, MT., Savoia, P., Quaglino, P., et al.[2019]

In a phase II study involving 61 patients with relapsed or refractory diffuse large B-cell lymphoma, coltuximab ravtansine showed an overall response rate of 43.9%, indicating moderate efficacy in this difficult-to-treat population.

The treatment was generally well tolerated, with common side effects including fatigue (30%) and nausea (23%), and serious adverse events were relatively low, suggesting a favorable safety profile for this antibody drug conjugate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. Trnĕný, M., Verhoef, G., Dyer, MJ., et al.[2019]

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]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

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. England pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]

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

Mosunetuzumab: First Approval. [2022]

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

A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma. [2020]

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

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. [2019]

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. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

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]