Glofitamab for Mantle Cell Lymphoma

(GLOBRYTE Trial)

Recruiting at 99 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must not be taking: Systemic therapy, BTK inhibitors

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine (BR), or lenalidomide with rituximab (R-Len) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL).

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.

What data supports the effectiveness of the drug Glofitamab for treating Mantle Cell Lymphoma?

Glofitamab has shown promise in treating Mantle Cell Lymphoma, especially in patients who have relapsed after CAR T therapy, with reports of increased CAR T cells and positive responses in some patients. Additionally, Glofitamab is effective in other types of B-cell lymphomas, suggesting potential benefits for Mantle Cell Lymphoma as well. ^{1 2 3 4 5}

What safety data exists for treatments related to Glofitamab for Mantle Cell Lymphoma?

The combination of rituximab and lenalidomide has been studied for mantle cell lymphoma, showing a good safety profile. Rituximab, when added to other treatments, did not significantly increase toxicity, although it may increase the risk of infections. Additionally, rituximab combined with thalidomide showed low toxicity, with some severe adverse events like thromboembolic events and neutropenia (low white blood cell count). ^{6 7 8 9 10}

How is the drug Glofitamab different from other treatments for mantle cell lymphoma?

Glofitamab is unique because it is a bispecific antibody that engages T-cells to target and kill cancer cells, specifically binding to CD20 on B-cells and CD3 on T-cells. This mechanism is different from traditional chemotherapy and offers a new option for patients who have relapsed after other treatments like CAR T-cell therapy. ^{1 2 3 11 12}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Bendamustine (Chemotherapy)
• Glofitamab (Monoclonal Antibodies)
• Lenalidomide (Immunotherapy)
• Rituximab (Monoclonal Antibodies)

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.

Participant Groups

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.

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

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 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]

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]

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]

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 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 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]

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]

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

Glofitamab: First Approval. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma. [2022]

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

Current status of targeted therapies for mantle cell lymphoma. [2021]

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

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2023]

6. England 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. [2023]

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

Current and emerging new treatment strategies for mantle cell lymphoma. [2019]

8. United States 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. [2019]

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

Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. [2021]

10. United States 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. [2023]

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

Glofitamab CD20-TCB bispecific antibody. [2022]

12. 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]