Glofitamab for Mantle Cell Lymphoma

(GLOBRYTE Trial)

Recruiting at 116 trial locations

Overseen By Reference Study ID Number: GO43878 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Systemic therapy, BTK inhibitors

Disqualifiers: Pregnancy, CNS disease, Cardiovascular, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 cycles (glofitamab) or up to 6 cycles (BR/R-Len), cycle length varies

182 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called glofitamab to determine its effectiveness for individuals with mantle cell lymphoma (MCL) that has recurred or not responded to other treatments. Researchers aim to assess whether glofitamab outperforms standard treatments like rituximab (an antibody therapy) combined with other drugs. This trial may suit those diagnosed with MCL who have tried at least one other treatment, including a BTK inhibitor, without success. As a Phase 3 trial, it represents the final step before FDA approval, providing access to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic therapy, BTK inhibitors, and corticosteroids, at least 2 weeks before starting the study treatment. If you're on any investigational cancer treatments, you must also stop those within 2 weeks or 5 half-lives before the trial.

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

Research has shown that glofitamab was tested for safety in patients with relapsed or refractory mantle cell lymphoma. In earlier studies, all patients experienced some side effects, but proper care generally managed these. Serious side effects occurred in about 78.3% of patients, with 15% experiencing very severe issues. Despite these risks, the treatment demonstrated promising effectiveness, encouraging those considering participation in clinical trials. ^{1 2 3 4 5}

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

Glofitamab is unique because it offers a novel approach for treating mantle cell lymphoma by targeting CD20, a protein found on the surface of cancerous B-cells. Unlike traditional treatments, which often involve chemotherapy combinations like bendamustine and rituximab or rituximab and lenalidomide, glofitamab is a bispecific antibody. This means it can simultaneously engage with both cancer cells and immune cells, potentially leading to more direct and effective destruction of cancerous cells. Researchers are excited about glofitamab because its innovative mechanism could enhance precision in attacking lymphoma cells while potentially reducing the side effects associated with conventional chemotherapy.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

Research shows that glofitamab, which participants in this trial may receive as monotherapy, can be very effective in treating relapsed or refractory mantle cell lymphoma (MCL). Studies have found that 82% of patients responded well to the treatment, with 77% experiencing complete remission, meaning their cancer significantly decreased or disappeared. The treatment's effects also last over time, known as durable remission. With proper care, the side effects are generally manageable. These encouraging results suggest that glofitamab could be a good option for treating this type of lymphoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for people with Mantle Cell Lymphoma who've had at least one prior treatment including a BTK inhibitor. They should have measurable cancer on a CT scan, be expected to live at least 12 more weeks, and be fairly active (ECOG status 0-2). HIV-positive individuals or those without adequate blood function cannot join.

Inclusion Criteria

My Mantle Cell Lymphoma (MCL) diagnosis is confirmed with specific genetic markers.

My condition worsened after the last treatment or didn't improve with the last treatment.

I have a tumor that can be measured on a CT scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either glofitamab monotherapy or investigator's choice of rituximab plus bendamustine or lenalidomide with rituximab

12 cycles (glofitamab) or up to 6 cycles (BR/R-Len), cycle length varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Glofitamab
• Lenalidomide
• Rituximab

Trial Overview The study tests Glofitamab alone against either Rituximab plus Bendamustine or Lenalidomide with Rituximab in patients whose MCL has returned or didn't respond after treatment. The goal is to see which option works better for these patients.

How Is the Trial Designed?

Group I: Glofitamab monotherapy Experimental Treatment 3 Interventions

Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days).

Group II: BR or R-Len Active Control 4 Interventions

Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.

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?

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

Published Research Related to This Trial

Mantle cell lymphoma, a rare type of non-Hodgkin lymphoma affecting mainly older adults, has seen advancements in understanding its molecular pathology and treatment options over the past decade.

Recent targeted therapies have shown promising results with good safety profiles, suggesting a shift towards developing less toxic treatment regimens and identifying biomarkers for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging new treatment strategies for mantle cell lymphoma. Humala, K., Younes, A.[2019]

In a study of 16 patients with relapsed/refractory mantle cell lymphoma, the combination of rituximab and thalidomide resulted in an 81% objective response rate, with 31% achieving complete responses.

The treatment demonstrated a median progression-free survival of 20.4 months and a 3-year survival rate of 75%, indicating significant antitumor activity and a relatively low toxicity profile, although some severe adverse events were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Kaufmann, H., Raderer, M., Wöhrer, S., et al.[2021]

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 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]

Mantle cell lymphoma (MCL) has historically had poorer treatment outcomes compared to other non-Hodgkin's lymphoma subtypes, with many patients being ineligible for intensive therapies due to age and health conditions.

Current research is focusing on developing targeted therapies, such as the mTOR inhibitor temsirolimus and combination regimens with bortezomib, to improve treatment efficacy while minimizing side effects for patients with relapsed MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of targeted therapies for mantle cell lymphoma. Chang, JE., Kahl, BS.[2021]

In two cases of mantle cell lymphoma patients who relapsed after CAR T therapy, treatment with the bispecific antibody glofitamab led to significant increases in circulating CAR T cells and objective responses, indicating potential efficacy in this challenging scenario.

Glofitamab therapy was well-tolerated with no significant side effects reported, suggesting it could be a safe treatment option for patients with relapsed mantle cell lymphoma after CAR T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma. Heini, AD., Bacher, U., Porret, N., et al.[2022]

In a Phase III study involving 139 patients with previously untreated mantle cell lymphoma, the addition of rituximab to the fludarabine and cyclophosphamide (FC) treatment did not significantly increase overall toxicity compared to FC alone.

While there was a higher rate of lymphocytopenia (low lymphocyte count) in the group receiving rituximab, this did not lead to an increase in febrile episodes or infections, suggesting that rituximab can be safely added to the treatment regimen without raising infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of fludarabine and cyclophosphamide with or without rituximab as initial therapy for patients with previously untreated mantle cell lymphoma: results of a randomised phase II study. Eve, HE., Linch, D., Qian, W., et al.[2019]

In a study of 103 patients with relapsed/refractory mantle cell lymphoma receiving CD19-directed CAR T-cell therapy (brexucabtagene autoleucel), those with a high baseline CAR-HEMATOTOX (HT) score experienced significantly worse outcomes, including prolonged neutropenia and a higher rate of severe infections.

Patients with high HT scores had a 1-year non-relapse mortality rate of 17% compared to 4.6% in those with low scores, and they also showed inferior progression-free survival and overall survival rates, highlighting the importance of the HT score in predicting treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Rejeski, K., Wang, Y., Albanyan, O., 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]

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]

The maximum tolerated dose (MTD) of lenalidomide when combined with rituximab for treating relapsed or refractory mantle-cell lymphoma (MCL) was determined to be 20 mg, with the combination showing a manageable safety profile despite some grade 3-4 hematological toxicities.

In a phase 2 trial involving 44 patients, the combination therapy resulted in a 57% overall response rate, with 36% achieving a complete response and a median overall survival of 24.3 months, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Wang, M., Fayad, L., Wagner-Bartak, N., 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39365960/

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02470

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma After a median follow-up of 19.6 (range, 0-39) months, 60 patients were efficacy-evaluable (one patient received no study treatment).

3. onclive.com onclive.com/view/glofitamab-produces-durable-remissions-in-r-r-mantle-cell-lymphoma

Glofitamab Produces Durable Remissions in R/R Mantle ... Glofitamab-gxbm monotherapy achieved an 82% overall response rate and 77% complete response rate in relapsed/refractory mantle cell lymphoma ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1631/531703/Glofitamab-Induces-High-Response-Rates-and-Durable

Glofitamab Induces High Response Rates and Durable ... Glofitamab Induces High Response Rates and Durable Remissions in Patients (Pts) with Heavily Pretreated Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) ...

5. roche.com roche.com/media/releases/med-cor-2025-05-23

New two-year follow-up of Roche's Columvi extends ... After a median follow-up of 24.7 months, data showed a 40% improvement in overall survival (OS) for patients treated with Columvi® (glofitamab) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06252675

NCT06252675 | Glofitamab With Pirtobrutinib for Relapsed ... This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma ...