Mosunetuzumab + Glofitamab for Non-Hodgkin's Lymphoma

Recruiting at 34 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

Trial Summary

What is the purpose of this trial?

This trial is testing new drug combinations to help the immune system fight B-cell Non-Hodgkin Lymphoma. The drugs work by helping the body recognize and attack cancer cells more effectively. A combination of two drugs has shown promise in treating non-Hodgkin lymphoma by enabling the immune system to recognize and attack cancer cells.

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.

What data supports the effectiveness of the drug Mosunetuzumab + Glofitamab for Non-Hodgkin's Lymphoma?

Research shows that Glofitamab, a part of this drug combination, has been effective in treating B-cell non-Hodgkin lymphoma, with studies indicating over 50% complete responses in heavily treated patients. It works by engaging T-cells to attack cancer cells, offering a promising option for patients with limited treatment choices. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Glofitamab safe for humans?

Glofitamab and Mosunetuzumab are both bispecific antibodies that have been conditionally approved for certain types of non-Hodgkin's lymphoma, indicating they have been evaluated for safety in humans. Glofitamab has been studied in a phase I trial with measures to reduce toxicity, and Mosunetuzumab has been approved based on clinical trials showing its effectiveness and safety profile. ^{1 3 6 7 8}

What makes the drug Mosunetuzumab + Glofitamab unique for treating Non-Hodgkin's Lymphoma?

Mosunetuzumab and Glofitamab are unique because they are bispecific antibodies that engage T-cells to target and kill cancer cells, offering a novel approach for patients with relapsed or refractory Non-Hodgkin's Lymphoma who have limited treatment options. These drugs have shown promising results in clinical trials, with Mosunetuzumab achieving high response rates and Glofitamab being effective even in patients who cannot undergo CAR T-cell therapy. ^{1 2 3 4 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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, 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]

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]

References

1. United States 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. [2023]

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

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

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

Glofitamab: First Approval. [2023]

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

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. [2022]

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

Glofitamab CD20-TCB bispecific antibody. [2022]

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

Mosunetuzumab: First Approval. [2022]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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