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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of lymphoma, including diffuse large B-cell lymphoma (DLBCL). Researchers aim to determine if the combination treatment, which includes glofitamab (a type of immunotherapy) and other medicines, is effective and has manageable side effects. This treatment may suit individuals aged 65 and older who have not received prior systemic treatment for their lymphoma. Participants must have a specific type of lymphoma that is measurable by scan and no serious heart conditions.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in lymphoma care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of glofitamab, obinutuzumab, and polatuzumab can be safely used in patients with diffuse large B-cell lymphoma (DLBCL). Specifically, glofitamab has demonstrated a 46% overall response rate in patients with difficult-to-treat forms of this cancer. However, more than half of the patients experienced serious side effects, classified as grade 3 or 4, during treatment.

These side effects indicate that the treatment can be intense, but they are considered manageable with proper medical care. Since glofitamab is already approved for use in certain cases of DLBCL, some existing safety information is available. This approval suggests it may be safe, though individual experiences can vary. It is essential to consult a healthcare provider to understand what these findings might mean for individual cases. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about glofitamab-based treatments for diffuse large B-cell lymphoma because they offer a novel approach by targeting CD20 and CD3 proteins, unlike traditional chemotherapy which broadly attacks cancer cells. Glofitamab, a bispecific antibody, helps direct the immune system to specifically attack lymphoma cells, potentially increasing precision and reducing side effects. Additionally, the combination with obinutuzumab and polatuzumab may enhance the immune response, offering a promising alternative to standard treatments like R-CHOP, which primarily rely on chemotherapy and rituximab.

What evidence suggests that this treatment might be an effective treatment for diffuse large B-cell lymphoma?

Research has shown that glofitamab, one of the treatments in this trial, holds promise for treating diffuse large B-cell lymphoma (DLBCL), especially when combined with other treatments. Studies have found that 52% of patients experienced their cancer shrinking or disappearing. Glofitamab helps the body's immune cells, called T-cells, find and destroy cancer cells. In this trial, glofitamab is used with polatuzumab, another cancer-fighting drug, and has proven effective even for patients whose cancer has returned or is difficult to treat. The treatment's side effects can be managed, making it a hopeful option for people with this aggressive type of lymphoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Pallawi Torka, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

Ability to comply with all the study-related procedures

My lymphoma is at an advanced stage.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... It is characterized by aggressive clinical behavior and poor outcomes in high-risk subgroups, particularly patients with diffuse large B-cell ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ... Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

3. 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.

4. 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.

5. oncologynurseadvisor.com oncologynurseadvisor.com/news/glofitamab-lymphoma-dlbcl-improve-outcomes-treatment-risk/

Glofitamab May Improve Outcomes in Patients With ... Researchers determined glofitamab may induce a complete response rate in 27% of real-world cases of relapsed or refractory DLBCL.

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

Safety and efficacy of glofitamab for relapsed/refractory ... Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07001540

Study Details | NCT07001540 | Evaluation of the Efficacy ... This is a prospective, multicenter, single-arm clinical study designed to evaluate the efficacy and safety of Polatuzumab Vedotin combined with Rituximab, ...