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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug glofitamab to determine if it can prevent diffuse large B-cell lymphoma, a type of blood cancer, from returning in patients who have responded well to their first round of standard treatment but still show signs of minimal residual disease (MRD). The study also aims to ensure the treatment's safety for participants. This trial might suit those who have completed a full course of initial chemotherapy, achieved a complete response, but still have MRD. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Studies have shown that glofitamab, a treatment for certain types of lymphoma, has been tested in patients whose large B-cell lymphoma returned or did not respond to previous treatments. These studies indicate that while the treatment can be effective, some safety concerns exist. Serious side effects occurred in about 48% of patients, with fatal reactions in 5%. Some patients experienced tumor flare, causing pain and swelling at the lymphoma site. Another significant risk is Cytokine Release Syndrome (CRS), where the immune system overreacts, which can be serious or even fatal. Patients need to take medication beforehand to help manage this risk. Despite these concerns, researchers consider the safety of glofitamab manageable for those who have already tried multiple treatments without success. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Glofitamab is unique because it targets CD20, a protein commonly found on the surface of B-cell lymphomas, using a novel bispecific antibody approach. This means it can simultaneously engage with both the cancer cells and T-cells, which are part of the immune system, to help destroy the cancer cells more effectively. Unlike standard treatments like rituximab, which also targets CD20 but through a single-target mechanism, glofitamab's dual-targeting action has the potential to enhance the immune response and improve outcomes for patients. Researchers are excited because this innovative mechanism may offer a more powerful and precise treatment option for lymphoma, potentially leading to better patient responses.

What evidence suggests that glofitamab might be an effective treatment for lymphoma?

Research has shown that glofitamab, the investigational treatment in this trial, may help treat certain aggressive types of lymphoma. In one study, 46% of patients responded to the treatment, and 27% had complete responses, meaning their cancer was no longer detectable. These results are promising for people with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). Another study found that glofitamab was effective for DLBCL, though some patients experienced serious side effects. Overall, these findings suggest that glofitamab could be a helpful treatment option for lymphoma, especially when other treatments have failed. ^{6 7 8 9 10}

Who Is on the Research Team?

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

Understand and sign a written informed consent document

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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 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]

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]

Citations

1. columvi-hcp.com columvi-hcp.com/efficacy/clinical-trial-results.html

COLUMVI™ (glofitamab-gxbm) efficacy | HCP Tumor flare was reported in 12% of patients who received COLUMVI, including Grade 2 tumor flare in 4.8% of patients and Grade 3 tumor flare in 2.8%.

2. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... A total of 201 of 245 patients (82.0%) were efficacy-evaluable (124 treated with epcoritamab [80%], and 77 treated with glofitamab [87%]).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39661985/

Safety and efficacy of glofitamab for relapsed/refractory ... The overall response rate was 46%, with 27% achieving complete responses (CR) and 19% partial responses. The median progression-free survival ( ...

4. columvi.com columvi.com/columvi-results/clinical-trial-results.html

Clinical trial results COLUMVI (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL)

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206913

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell ... Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

6. columvi-hcp.com columvi-hcp.com/safety/important-safety-information.html

COLUMVI™ (glofitamab-gxbm) Important Safety Information COLUMVI can cause serious tumor flare. Manifestations included localized pain and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural ...

7. columvi.com columvi.com/side-effects/important-safety-information.html

Indication and Important Safety Information Important safety information for COLUMVI™ (glofitamab-gxbm) including indication, dosing, and possible side effects. See important safety including Serious ...

8. gene.com gene.com/medical-professionals/medicines/columvi

Columvi® (glofitamab-gxbm) - Information for Healthcare ... Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving COLUMVI. Premedicate before each dose, and initiate ...

9. columvi-hcp.com columvi-hcp.com/safety/summary.html

COLUMVI™ (glofitamab-gxbm) side effects | HCP COLUMVI™ safety profile · Serious adverse reactions occurred in 48% of patients who received COLUMVI. · Fatal adverse reactions occurred in 5% of patients from ...

10. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3865/534578/Safety-and-efficacy-of-glofitamab-for-relapsed

Safety and efficacy of glofitamab for relapsed/refractory large ... Glofitamab has a 46% ORR (27% CR; 19% PR) and a manageable safety in heavily pretreated patients with r/r LBCL.