Mosunetuzumab + Glofitamab for Non-Hodgkin's Lymphoma

Recruiting at 38 trial locations

Overseen By Reference Study ID Number: CO43805 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: Cereblon modulators

Disqualifiers: Pregnancy, CNS lymphoma, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

121 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatment combinations to assess their safety and effectiveness for individuals with B-cell Non-Hodgkin's Lymphoma, a cancer affecting the immune system. The study evaluates how well two drugs, mosunetuzumab and glofitamab, perform when combined with either CC-220 (Iberdomide) or CC-99282. Participants suitable for this trial have lymphoma that has returned or not responded to at least one prior treatment and require further systemic therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive these new therapies.

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, it mentions that certain treatments and medications should not be taken close to the start of the trial, such as radiotherapy within 2 weeks or chemotherapy within 4 weeks. 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?

A previous study found that mosunetuzumab has a relatively mild safety profile. Some patients experienced cytokine release syndrome (CRS), where the immune system becomes very active, but this was manageable. Researchers are investigating the safety of combining CC-220 with mosunetuzumab, though detailed results are not yet available.

For the combination of mosunetuzumab with CC-99282, mosunetuzumab has been studied in other trials and is generally well-tolerated. However, like any treatment, it can have side effects.

Glofitamab is another treatment in the study. It has been used in patients with a type of lymphoma before, and no new safety concerns emerged. The safety of combining it with CC-99282 is still under study, but no major issues have been identified so far.

Overall, as this is a phase 1 trial, the main goal is to understand the safety and best dose. Reaching this phase usually indicates that earlier tests suggested it might be safe enough to try in more people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which typically involve chemotherapy and monoclonal antibodies, mosunetuzumab and glofitamab offer a novel approach by engaging the body's own immune system more directly. Mosunetuzumab is a bispecific antibody that can bind to both the cancer cells and T-cells, essentially guiding the immune cells to attack the cancer. Glofitamab works similarly but is designed for intravenous delivery, which could potentially enhance its effectiveness and convenience for certain patients. Researchers are excited about these treatments because they represent a new way to activate the immune system against cancer, potentially leading to more targeted and effective outcomes.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that mosunetuzumab, which participants in this trial may receive with CC-220 or CC-99282, has achieved impressive results in patients with hard-to-treat lymphoma. Patients receiving this treatment have experienced long-lasting remissions, averaging about 22.8 months.

Glofitamab, another treatment option in this trial, has been approved for certain types of non-Hodgkin's lymphoma. It has demonstrated that patients can live without disease progression for an average of 8 months, with an average overall survival time of 11 months.

The CELMoDs, CC-220 and CC-99282, are under study to determine if they can enhance these treatments' effectiveness, although specific results for these drugs alone remain limited. The combinations tested in this trial may offer new hope for patients with B-cell non-Hodgkin's lymphoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with B-cell Non-Hodgkin Lymphoma who've had at least two prior treatments can join this trial. They must have a measurable tumor, be in fair health (ECOG 0-2), and not planning to get pregnant or father a child. People can't join if they've had certain recent treatments, live vaccines, CNS lymphoma, severe allergies to monoclonal antibodies, unresolved toxicities from past treatments, significant other diseases, or are pregnant.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

Availability of a representative tumor specimen and pathology report

My blood counts are within a healthy range.

Exclusion Criteria

I have received specific treatments before.

Severe allergic or anaphylactic reactions to monoclonal antibody therapy

History of autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab or glofitamab in combination with CC-220 and/or CC-99282

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CC-220
• CC-99282
• Glofitamab
• Mosunetuzumab

Trial Overview The study tests the safety and effectiveness of mosunetuzumab or glofitamab combined with CELMoDs (CC-220 or CC-99282) for treating B-cell NHL. It will also look at how the body processes these drugs. Participants will receive one combination of these medications through IV or subcutaneous injections.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 4 Interventions

Participants will receive intravenous (IV) glofitamab + CC-99282.

Group II: Arm 1 Experimental Treatment 4 Interventions

Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Glofitamab is a promising new treatment for B cell lymphomas that do not respond to standard R-CHOP chemotherapy, which fails in over one-third of cases.

As a bispecific antibody targeting CD20 and CD3, glofitamab works by engaging T cells to attack tumor cells, offering a novel approach for patients with relapsed or refractory lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. Wang, C., Liu, Y.[2023]

Glofitamab, a bispecific antibody, demonstrated a 53.8% overall response rate in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with a complete response rate of 36.8%, indicating its efficacy in a heavily pretreated population.

The treatment had a manageable safety profile, with cytokine release syndrome occurring in 50.3% of patients but mostly at lower grades, and only 2.9% of patients withdrew due to adverse events, suggesting that glofitamab can be safely administered with prior obinutuzumab pretreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. Hutchings, M., Morschhauser, F., Iacoboni, G., et al.[2023]

Glofitamab, a bispecific monoclonal antibody targeting CD20 and CD3, was conditionally approved in Canada on March 25, 2023, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone multiple prior therapies and are ineligible for CAR T-cell therapy.

The drug is currently under regulatory review in the EU and USA, with ongoing clinical development as both a standalone treatment and in combination with other therapies for non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. Shirley, M.[2023]

Glofitamab, a bispecific antibody targeting CD20 and CD3, demonstrated clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma during a phase 1 trial, showing T-cell activation and tumor cell killing.

The study identified that tumor intrinsic factors, such as TP53 signaling, may contribute to resistance against glofitamab, indicating that these factors could serve as important biomarkers for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Bröske, AE., Korfi, K., Belousov, A., et al.[2022]

Glofitamab is a novel bispecific T-cell recruiting antibody that targets both CD20 on B-cells and CD3 on T-cells, showing over 50% complete response rates in heavily treated patients with aggressive and indolent B-cell lymphoma during Phase 1 trials.

The unique 2:1 configuration of glofitamab allows for an extended half-life and superior binding to CD20, making it a promising option for patients with limited treatment choices, with ongoing trials evaluating its efficacy in combination therapies and earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. Minson, A., Dickinson, M.[2022]

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]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, with manageable side effects; however, cytokine release syndrome was common (49.7%), and there was one reported fatality due to immune effector cell-associated neurotoxicity syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Thieblemont, C., Phillips, T., Ghesquieres, H., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10245362/

Glofitamab: First Approval - PMC - PubMed Central Median IRC-assessed PFS was 8 months (95% CI 3 to not reached) and median overall survival was 11 months (95% CI 9 to not reached) [10].

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05169515

NCT05169515 | A Study Evaluating the Safety, ... This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 and/or CC-99282) in ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2025.2486437

Glofitamab results in cost savings versus epcoritamab ... Glofitamab is approved by the US Food and Drug Administration (FDA) for the treatment of adults with R/R DLBCL not otherwise specified or large B-cell lymphoma ...

4. blogs.the-hospitalist.org blogs.the-hospitalist.org/content/lbcl-bispecific-antibodies-fare-less-well-real-world-analysis

Bispecific Antibodies Fare Less Well in Real-World Analysis The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%). The ...

5. everyone.org everyone.org/explore/compare?id1=556&id2=568

Epkinly (epcoritamab-bysp) vs Columvi (glofitamab-gxbm) Efficacy of Epkinly (epcoritamab-bysp) in Lymphoma​​ Clinical trials have demonstrated promising efficacy in patients with relapsed or refractory non-Hodgkin ...

6. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/non-hodgkin-lymphoma

Non-Hodgkin Lymphoma Clinical Trials A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed or Refractory Non-Hodgkin ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761324Orig1s000MultidisciplineR.pdf

761324Orig1s000 - accessdata.fda.gov Conduct an integrated safety analysis of data from patients with large B-cell lymphoma and other lymphoid malignancies to further ...

8. ema.europa.eu ema.europa.eu/en/documents/rmp/columvi-epar-risk-management-plan_en.pdf

EU RISK MANAGEMENT PLAN FOR COLUMVI/GLOFITAMAB of glofitamab in patients with relapsed/refractory B-cell non-Hodgkin's lymphoma ... laboratory data and vital signs, with no new safety signals.