Glofitamab + Chemoimmunotherapy for B-Cell Lymphoma

(iMATRIX GLO Trial)

Recruiting at 31 trial locations

Overseen By Reference Study ID Number: CO43810 https://forpatients.roche.com

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Live vaccines

Disqualifiers: CNS disease, Active infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: 21

Duration: 9-36 weeks

65 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have ongoing adverse events from prior anti-cancer therapy and should not have active infections. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Glofitamab + Chemoimmunotherapy for B-Cell Lymphoma?

Research shows that adding monoclonal antibodies like rituximab to chemotherapy improves response rates and survival in various types of B-cell lymphomas, such as diffuse large B-cell lymphoma and follicular lymphoma. This suggests that combining monoclonal antibodies with chemotherapy can be effective in treating B-cell lymphomas. ^{1 2 3 4 5}

What makes the drug Glofitamab unique for treating B-cell lymphoma?

Glofitamab is unique because it is a bispecific antibody that targets both CD20 on B cells and CD3 on T cells, helping the immune system attack cancer cells. It is particularly used for patients with relapsed or refractory B-cell lymphoma who have limited treatment options, especially those who cannot undergo CAR T-cell therapy. ^{6 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Eligibility Criteria

This trial is for young individuals, from 6 months to under 18 years old (up to ≤30 years for part of the study), with relapsed/refractory mature B-cell non-Hodgkin lymphoma. They must have had previous standard chemoimmunotherapy and show measurable disease. Good performance status and organ function are required, without active infections like HBV, HCV, or HIV.

Inclusion Criteria

My condition did not improve after standard cancer treatment.

I am between 6 months and 18 years old for part 1, and up to 30 years old for part 2.

My bone marrow, liver, and kidneys are functioning well.

Exclusion Criteria

I do not have any ongoing infections.

I have been diagnosed with progressive multifocal leukoencephalopathy.

I have not had major surgery or a significant injury in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles or glofitamab monotherapy for up to 12 cycles

9-36 weeks

Visits every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Carboplatin
• Etoposide
• Glofitamab
• Ifosfamide
• Obinutuzumab
• Rituximab
• Tocilizumab

Trial Overview The trial tests glofitamab alone and combined with R-ICE chemoimmunotherapy (rituximab, ifosfamide, carboplatin, etoposide) in children and young adults who've seen their B-cell lymphoma return or resist treatment. It aims to assess safety and effectiveness.

Participant Groups

Group I: Arm B Experimental Treatment 3 Interventions

Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).

Group II: Arm A Experimental Treatment 7 Interventions

Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

The addition of rituximab, a monoclonal antibody, to conventional chemotherapy (R-CHOP regimen) significantly enhances treatment outcomes for patients with diffuse large B-cell lymphoma (DLBCL), improving response rates, progression-free survival (PFS), and overall survival (OS).

Rituximab also boosts response rates and PFS in mantle cell lymphoma (MCL) and improves outcomes in follicular lymphoma (FL), highlighting its critical role in enhancing the efficacy of chemotherapy across various types of non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. Kahl, B.[2021]

In a study involving 549 patients with advanced indolent lymphoma, bendamustine plus rituximab significantly improved median progression-free survival (69.5 months) compared to R-CHOP (31.2 months), indicating it may be a more effective first-line treatment.

Bendamustine plus rituximab was better tolerated than R-CHOP, with significantly lower rates of side effects such as alopecia, hematological toxicity, infections, and peripheral neuropathy, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Rummel, MJ., Niederle, N., Maschmeyer, G., et al.[2022]

In a study of 57 patients with untreated mantle-cell lymphoma, a treatment regimen of four cycles of R-CHOP followed by yttrium-90 (90Y)-ibritumomab tiuxetan resulted in an overall response rate of 82%, indicating strong efficacy.

The median time to treatment failure was 34.2 months, and the estimated 5-year overall survival rate was 73%, demonstrating that this combination therapy is well-tolerated and offers promising outcomes compared to historical data with six cycles of R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499. Smith, MR., Li, H., Gordon, L., et al.[2021]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

In a phase II trial involving 39 patients with untreated follicular lymphoma, the combination of bendamustine and rituximab (BR) followed by consolidation with Yttrium-90 Ibritumomab tiuxetan (90YIT) achieved a high response rate of 94.8%, with 77% of patients reaching complete response or unconfirmed complete response.

The treatment regimen demonstrated durable results, with a median progression-free survival of 45 months and an impressive 81% conversion rate from partial response to complete response after 90YIT, indicating it is a safe and effective frontline therapy for follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, Open-Label, Phase II Study of Bendamustine and Rituximab Followed by 90-Yttrium (Y) Ibritumomab Tiuxetan for Untreated Follicular Lymphoma (Fol-BRITe). Lansigan, F., Costa, CA., Zaki, BI., et al.[2020]

In a study analyzing overall survival (OS) for five treatments of relapsed-refractory diffuse large B-cell lymphoma (DLBCL), tafasitamab plus lenalidomide showed the best OS with a median of 26.5 months and a hazard ratio of 0.514 compared to glofitamab, indicating it may be a more effective option.

Despite glofitamab's advanced mechanism as a bispecific antibody, it did not demonstrate a significant OS advantage over the other treatments, with a median survival of 11.7 months, suggesting that other therapies may be more beneficial for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for Relapsed-Refractory Diffuse Large B-cell Lymphoma: A Preliminary Evaluation of the Place in Therapy of Glofitamab, a Bispecific Monoclonal Antibody. Messori, A., Rivano, M., Mengato, D., et al.[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]

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, 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

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. [2022]

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

Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499. [2021]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]

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

Multicenter, Open-Label, Phase II Study of Bendamustine and Rituximab Followed by 90-Yttrium (Y) Ibritumomab Tiuxetan for Untreated Follicular Lymphoma (Fol-BRITe). [2020]

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

Treatments for Relapsed-Refractory Diffuse Large B-cell Lymphoma: A Preliminary Evaluation of the Place in Therapy of Glofitamab, a Bispecific Monoclonal Antibody. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Glofitamab: First Approval. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. [2023]

10. 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]