Glofitamab for Lymphoma

Overseen By Dai Chihara, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anthracycline-based chemoimmunotherapy

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Relapsed disease, CNS lymphoma, HIV, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

30 Participants Needed

Trial Summary

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, if you are on chronic corticosteroids or immunosuppressive therapy, you may need to adjust your treatment as these are generally excluded unless at low doses. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Glofitamab for lymphoma?

Glofitamab has shown promising results in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with some patients achieving complete or partial responses. In a real-world study, the median overall survival was 8.8 months, and the estimated 1-year progression-free survival rate was 83% for treatment-responsive patients. ^{1 2 3 4 5}

Is Glofitamab safe for humans?

Glofitamab has been studied for safety in people with B-cell lymphomas. Some patients experienced serious side effects, including cytokine release syndrome (a severe immune reaction) and febrile neutropenia (fever with low white blood cell count), which led to deaths in a few cases. However, these side effects are not experienced by everyone, and the treatment has shown promise in patients who have limited options. ^{1 2 3 5 6}

What makes the drug Glofitamab unique for treating lymphoma?

Glofitamab is unique because it is a bispecific antibody that simultaneously targets CD20 on B cells and CD3 on T cells, helping the immune system attack cancer cells. Its novel 2:1 structure allows for better binding and a longer half-life, making it a promising option for patients with relapsed or refractory B-cell lymphomas who have limited treatment options. ^{1 2 3 5 6}

What is the purpose of this trial?

The goal of this clinical research study is to learn if glofitamab can help to prevent recurrence of LBCL in patients who have achieved CR after standard first-line therapy but have tested positive for MRD. The safety of glofitamab will also be studied.

Research Team

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with certain types of large B-cell lymphoma who've had a complete response to first-line therapy but still have minimal residual disease (MRD). They must be in good health, understand the study, and agree to use contraception. Excluded are those with significant heart issues, recent surgeries or transfusions, other cancers within 3 years, severe allergies to therapies, immune conditions or treatments that could interfere.

Inclusion Criteria

My cancer responded completely to the first treatment according to Lugano criteria.

Understand and sign a written informed consent document

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

Exclusion Criteria

I have a serious heart condition.

I have not had a recent blood transfusion or taken any experimental drugs.

I have had surgery recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glofitamab to determine the rate of undetectable MRD and evaluate safety

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Glofitamab

Trial Overview The trial is testing Glofitamab's effectiveness in preventing the return of large B-cell lymphoma after initial successful treatment. Participants must have achieved complete remission but show MRD presence. The safety profile of Glofitamab will also be evaluated during this phase.

Participant Groups

Group I: Glofitamab Experimental Treatment 1 Intervention

Participants will enter a screening period to determine eligibility for the study

Glofitamab is already approved in United States for the following indications:

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

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]

In a real-world study of 43 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with glofitamab, the median overall survival was 8.8 months, indicating promising efficacy in a heavily pretreated population.

However, the study also highlighted significant safety concerns, with treatment-related deaths occurring due to cytokine release syndrome and febrile neutropenia, emphasizing the need for careful monitoring of hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. Birtas Atesoglu, E., Gulbas, Z., Uzay, A., 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 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, 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 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]

References

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

Glofitamab: First Approval. [2023]

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

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. [2023]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Glofitamab CD20-TCB bispecific antibody. [2022]