Glofitamab-Based Treatment for Diffuse Large B-Cell Lymphoma

Recruiting at 6 trial locations

Overseen By Paul Hamlin, MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Monoclonal antibodies

Disqualifiers: Prior transplants, Active CNS involvement, Uncontrolled infections, Cardiovascular 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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 24 weeks

42 Participants Needed

Trial Summary

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 corticosteroids, you may need to adjust the dose as per the trial's guidelines. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Glofitamab for treating diffuse large B-cell lymphoma?

Glofitamab has shown promising results in treating diffuse large B-cell lymphoma, especially in patients who have not responded to other treatments. In a study, 21% of patients achieved complete response, and 16% had a partial response, with a median overall survival of 9 months, indicating its potential effectiveness in difficult-to-treat cases. ^{1 2 3 4 5}

Is glofitamab safe for humans?

Glofitamab has been studied for safety in patients with diffuse large B-cell lymphoma, and while it shows promise, there are safety concerns. Some patients experienced serious side effects like 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. ^{1 2 3 4 6}

How is the drug Glofitamab unique for treating diffuse large B-cell lymphoma?

Glofitamab is unique because it is a bispecific antibody that engages T-cells to target and destroy cancer cells, specifically designed for patients with diffuse large B-cell lymphoma who have relapsed or are resistant to other treatments. It offers a novel approach by recruiting the body's own immune cells to fight the cancer, which is different from traditional chemotherapy. ^{1 2 3 4 5}

What is the purpose of this trial?

The researchers are doing this study to find out if the study treatment is an effective treatment that causes few or mild side effects in people with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), or transformed lymphoma. The treatment being tested in this study is glofitamab, polatuzumab, and obinutuzumab in combination with standard treatment (the combination of rituximab, cyclophosphamide, doxorubicin, and prednisone, or R-miniCHP).

Research Team

Pallawi Torka, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals with certain types of lymphoma, including diffuse large B-cell lymphoma. Participants should be suitable for the study treatments and have not been treated with similar drugs before. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

My lymphoma is at an advanced stage.

Ability to comply with all the study-related procedures

I am between 65-79 years old and considered unfit or frail.

Exclusion Criteria

I haven't had cancer treatment with monoclonal antibodies in the last 3 months.

I haven't taken any experimental cancer treatments in the last 28 days.

I have not had systemic therapy for lymphoma, but may have had radiation, steroids, or antibiotics.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 cycles of glofitamab and polatuzumab followed by an interim PET scan. Based on the scan results, they receive either 4 or 6 cycles of glofitamab-pola-R-miniCHP.

Approximately 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Glofitamab

Trial Overview The study tests a combination of glofitamab, polatuzumab, and obinutuzumab with standard treatment (rituximab, cyclophosphamide, doxorubicin, prednisone) to see if it's effective and has mild side effects in treating specific lymphomas.

Participant Groups

Group I: Obinutuzumab, Glofitamab and Polatuzumab Experimental Treatment 6 Interventions

All patients will receive 2 cycles of glofitamab and polatuzumab followed by an interim PET scan (iPET2). If iPET2 is negative (Deauville score 1-3), patients will receive 4 cycles of glofitamab-polaRminiCHP. If iPET is positive (Deauville score 4,5) with partial response or stable disease, patients will receive 6 cycles of glofitamab-pola-R-miniCHP (polatuzumab will be omitted from last 2 cycles to keep total number of doses at 6 per standard of care)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

In a phase 2 study involving 155 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), glofitamab treatment resulted in a complete response in 39% of patients, demonstrating its efficacy as a therapy.

While glofitamab showed promising results, 62% of patients experienced adverse events of grade 3 or higher, with cytokine release syndrome being the most common, affecting 63% of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Dickinson, MJ., Carlo-Stella, C., Morschhauser, F., 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]

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, 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 study of nine patients with diffuse large B-cell lymphoma (DLBCL) who relapsed after CAR T-cell therapy, the bispecific antibody glofitamab showed a promising overall response rate of 67%, with four patients achieving complete remission.

Glofitamab treatment was well tolerated, with only two cases of grade 2 cytokine release syndrome, and it appeared to enhance the persistence of residual CAR T-cells in some patients, suggesting a potential synergistic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy. Rentsch, V., Seipel, K., Banz, Y., 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]

References

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

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Glofitamab: First Approval. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy. [2022]

6. 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]