Mosunetuzumab for Non-Hodgkin's Lymphoma

(MorningSun Trial)

Not currently recruiting at 57 trial locations

Overseen By Reference Study ID Number: ML43389 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: CNS disease, Autoimmune disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 34 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mosunetuzumab (also known as Lunsumio), a new treatment for certain types of non-Hodgkin's lymphoma, a cancer affecting the lymphatic system. The trial aims to evaluate the treatment's effectiveness and safety. Participants will include those with untreated or treatment-resistant forms of the disease, such as diffuse large B-cell lymphoma or follicular lymphoma. Ideal candidates have a measurable tumor and are dealing with these specific types of lymphoma. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain treatments like monoclonal antibodies or immunosuppressive medications, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that mosunetuzumab is likely to be safe for humans?

Research has shown that mosunetuzumab is generally well-tolerated by people with various types of non-Hodgkin's lymphoma. For patients with diffuse large B-cell lymphoma (DLBCL), studies indicate that mosunetuzumab is both effective and tolerable, with some patients experiencing long-term survival benefits.

In marginal zone lymphoma (MZL) cases, mosunetuzumab led to lasting responses, demonstrating long-term effectiveness. Reports noted that side effects were manageable and could be handled without much difficulty.

Patients with follicular lymphoma (FL) experienced long-lasting remissions after treatment with mosunetuzumab, with their cancer remaining in remission for extended periods and side effects considered manageable.

For transformed follicular lymphoma (tFL) and Richter's transformation (RT), mosunetuzumab maintained a manageable safety profile, with side effects that could be effectively managed.

Lastly, in mantle cell lymphoma (MCL), mosunetuzumab showed promising results, with side effects that patients could handle. Although some treatment-related side effects occurred, they remained within a manageable range.

Overall, the treatment appears well-tolerated across various types of non-Hodgkin's lymphoma, with generally manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-Hodgkin's lymphoma?

Mosunetuzumab is unique because it offers a new approach to treating various types of non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma, marginal zone lymphoma, follicular lymphoma, Richter's transformation, and mantle cell lymphoma. Unlike traditional therapies, which often involve chemotherapy, mosunetuzumab is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells. This dual-targeting mechanism helps the body's own immune system recognize and attack cancer cells more effectively. Researchers are excited about this treatment because it is administered subcutaneously, potentially offering a more convenient and less invasive option compared to standard intravenous treatments. This novel mechanism and delivery method might provide a promising alternative for patients with these challenging conditions.

What evidence suggests that mosunetuzumab could be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that mosunetuzumab can effectively treat different types of non-Hodgkin's lymphoma. In this trial, participants with diffuse large B-cell lymphoma (DLBCL) will receive mosunetuzumab, which past studies have shown to achieve about 24% complete responses. For those with marginal zone lymphoma (MZL), mosunetuzumab demonstrated an overall response rate of 77.8%, with 63.9% of patients experiencing significant tumor reduction or disappearance. Participants with follicular lymphoma (FL) will also receive mosunetuzumab, which previous research has shown to achieve an overall response rate of about 80%, with long-lasting remissions. Additionally, mosunetuzumab showed promising results in mantle cell lymphoma (MCL), with an overall response rate of 88% and complete responses in 79% of cases. These findings suggest that mosunetuzumab could be a strong option for treating various B-cell cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with certain types of non-Hodgkin's lymphoma who have measurable disease, adequate organ function, and no severe infections or recent major surgeries. Participants must not be pregnant, agree to use contraception, and have a performance status that allows daily activity. Those with HIV can join if stable on therapy. It excludes those with past CNS lymphoma, recent monoclonal antibody treatment, active hepatitis B/C or other significant diseases.

Inclusion Criteria

My cancer type is confirmed by lab tests, I meet specific treatment history, kidney function, and lymphocyte count criteria.

I do not have any current infections.

My cancer type is confirmed by lab tests, I have a specific treatment history, and my kidneys work well.

Exclusion Criteria

I have no severe allergies to antibodies, no PML, and no active COVID-19.

Known or suspected chronic active Epstein-Barr virus (CAEBV) infection, history of macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH), positive test results for specific infections, or prior organ transplants

I have had brain lymphoma or cancer spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SC mosunetuzumab monotherapy for up to 17 or 34 cycles depending on the cohort, or until disease progression, study discontinuation, or death

Approximately 34 months

Maintenance Therapy

Participants achieving complete or partial metabolic response may receive maintenance therapy with mosunetuzumab every 8 weeks for 1 year

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab

Trial Overview The study tests mosunetuzumab's effects on various B-cell malignancies when administered under the skin (subcutaneous). Some participants may also receive tocilizumab. The trial aims to understand how well mosunetuzumab works alone in different doses and its safety profile.

How Is the Trial Designed?

Group I: Cohort E Experimental Treatment 2 Interventions

Participants with R/R Richter's transformation (RT), or R/R transformed follicular lymphoma (tFL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group II: Cohort D Experimental Treatment 2 Interventions

Participants with relapsed or refractory (R/R) mantle cell lymphoma (MCL) will receive SC mosunetuzumab monotherapy for up to 34 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group III: Cohort C Experimental Treatment 2 Interventions

Participants with untreated marginal zone lymphoma (MZL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group IV: Cohort B Experimental Treatment 2 Interventions

Elderly participants with untreated diffuse large B-cell lymphoma (DLBCL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first.

Group V: Cohort A Experimental Treatment 2 Interventions

Participants with high tumor burden with untreated follicular lymphoma (FL) will receive SC mosunetuzumab monotherapy for up to 17 cycles or until radiographic disease progression, study discontinuation, or death, whichever occurs first. Participants that achieve complete or partial metabolic response will have the option of receiving maintenance therapy with mosunetuzumab every 8 weeks for 1 year.

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?

Genentech, Inc.

Lead 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

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 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 I study involving 23 Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, mosunetuzumab was found to be well tolerated, with no deaths reported and manageable side effects, primarily neutropenia and cytokine release syndrome.

The treatment showed promising antitumor activity, with 2 patients achieving complete responses and 11 achieving partial responses, indicating its potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Munakata, W., Izutsu, K., Mishima, Y., et al.[2023]

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., 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]

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 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.

The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde, LE., Sehn, LH., Matasar, M., et al.[2022]

Citations

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

safety and efficacy results from a phase 2 study Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the ...

2. 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 ... Median progression-free survival was 24.0 months (95% CI, 12.0 to NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) ...

3. roche.com roche.com/media/releases/med-cor-2025-06-20

Roche's Lunsumio and Polivy combination significantly ... The Lunsumio and Polivy combination demonstrated a 59% reduction in risk of disease progression or death compared to R-GemOx.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19013

Efficacy and safety of mosunetuzumab-based regimens as ... Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to ...

5. ashpublications.org ashpublications.org/bloodadvances/article/7/17/4926/495381/Mosunetuzumab-monotherapy-is-active-and-tolerable

Mosunetuzumab monotherapy is active and tolerable in ... Mosunetuzumab is active as a single agent and yields CRs in 24% of heavily pretreated patients with R/R DLBCL.