Mosunetuzumab + Chemotherapy for B-Cell Lymphoma

Not currently recruiting at 1 trial location

Overseen By Nancy L. Bartlett

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants

Disqualifiers: CNS disease, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with aggressive B-cell lymphoma that has returned or stopped responding to previous treatments. The trial aims to determine if adding mosunetuzumab (a type of immunotherapy) to common chemotherapy regimens (DHAX or ICE) can be used safely and work better than existing treatments. Participants are divided into two groups based on the chemotherapy their doctor selects. Those who have already tried at least one line of chemotherapy but still have relapsed or resistant B-cell lymphoma might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that mosunetuzumab, when combined with chemotherapy treatments like DHAX or ICE, shows promising results for treating aggressive B-cell lymphomas. Earlier studies found that mosunetuzumab alone helped about 40% of patients with this type of cancer, with nearly half experiencing some improvement.

Regarding safety, previous research found that mosunetuzumab is generally well-tolerated by patients. Common side effects include fever and chills, but these are usually manageable. It's important to note that any chemotherapy treatment can have side effects, and this combination is no different. Ongoing research focuses on understanding how well patients cope with this specific combination with mosunetuzumab.

Although this trial is still in its early stages, the combination of mosunetuzumab with chemotherapy is being tested due to these encouraging safety and effectiveness results. Mosunetuzumab is a promising treatment, and its use with chemotherapy might offer a new option for those with relapsed or hard-to-treat B-cell lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mosunetuzumab combined with chemotherapy for treating B-cell lymphoma because it introduces an innovative approach by harnessing the immune system. Unlike standard chemotherapy options like R-CHOP or bendamustine, Mosunetuzumab is a bispecific antibody that targets CD20 on B-cells and CD3 on T-cells, effectively bridging immune cells with cancer cells to enhance the body's natural ability to fight the lymphoma. This mechanism of action is different from traditional treatments, which primarily work by directly attacking cancer cells. Additionally, the potential for integrating Mosunetuzumab with existing chemotherapy regimens like DHAX or ICE offers a new layer of personalized therapy, potentially leading to more effective and tailored treatment outcomes.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research has shown that mosunetuzumab, when combined with strong chemotherapy, may help treat aggressive B-cell lymphoma that has returned or is unresponsive to treatment. In this trial, participants will receive mosunetuzumab with either ICE or DHAX chemotherapy. Studies have found that about 35% of patients with aggressive cases and 66% with slow-growing cases respond to this treatment. In about 19% of these patients, the cancer becomes undetectable. For those treated with mosunetuzumab alone, about 40% responded, and nearly 24% had no detectable cancer. These results suggest that adding mosunetuzumab to chemotherapy might improve outcomes for patients with this type of lymphoma. ^{2 3 4 6 7}

Who Is on the Research Team?

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

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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.

Normal laboratory values

Agreement to use adequate contraception

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DHAX
• ICE
• Mosunetuzumab

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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 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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-09837

Mosunetuzumab in Combination with Platinum-Based ... Giving mosunetuzumab and DHAX or ICE may work better in treating patients with relapsed or refractory aggressive B cell lymphoma.

2. withpower.com withpower.com/trial/phase-1-diffuse-large-b-cell-lymphoma-dlbcl-9-2022-518be

Mosunetuzumab + Chemotherapy for B-Cell Lymphoma 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% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10913711/

Trial watch: bispecific antibodies for the treatment of ... Eighty-eight patients received IV mosunetuzumab at the dose of 30 mg, achieving an ORR and CR rate of 40% and 23.9%, respectively. CR rates were ...

4. ashpublications.org ashpublications.org/blood/article/141/5/467/486966/Bispecific-antibodies-for-the-treatment-of-B-cell

Bispecific antibodies for the treatment of B-cell lymphoma The median DOR and PFS were 22.8 months and 17.9 months, respectively, and the estimated 18-month OS rate was 90%.43 These data led to the ...

5. mdpi.com mdpi.com/2072-6694/17/15/2517

Targeted Therapies and Immunotherapies for Diffuse ... In a phase 1b/2 trial, Mosun-Pola achieved an ORR of 59% and a CR rate of 45.9%, with responses observed in patients previously treated with CAR-T therapy [38].

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05464329

Study Details | NCT05464329 | Mosunetuzumab in ... The hypothesis of this study is that mosunetuzumab can be safely combined with platinum-based salvage chemotherapy in this patient population, and that this ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37581593/

safety and efficacy results from a phase 2 study Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study