Glofitamab + Chemoimmunotherapy for B-Cell Lymphoma

(iMATRIX GLO Trial)

Recruiting at 40 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called glofitamab to determine its safety and effectiveness in treating B-cell non-Hodgkin lymphoma, a type of blood cancer. The trial involves two approaches: some participants will receive glofitamab combined with a common chemoimmunotherapy treatment, while others will receive only glofitamab. Suitable candidates for this trial include those whose B-cell non-Hodgkin lymphoma has returned or not responded to previous treatments. As a Phase 1 and Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Research has shown that glofitamab, when used alone, is approved for treating certain aggressive B-cell lymphomas. This approval indicates it has undergone safety testing in people. Some reported side effects include low blood cell counts and infections.

Studies have indicated that when glofitamab is combined with R-ICE chemoimmunotherapy, it has a manageable safety profile. While side effects exist, they can usually be controlled. Common issues include nausea and low blood cell counts.

Both treatments are being tested in early-stage trials, so more information about their safety is needed. However, existing research suggests they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about glofitamab for treating B-cell lymphoma because it represents a novel approach compared to traditional treatments, such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) and R-CHOP (Rituximab plus CHOP). Glofitamab is a bispecific antibody, which means it simultaneously binds to CD20 on B-cells and CD3 on T-cells, effectively recruiting the body's immune system to attack the cancer cells directly. This dual-targeting mechanism is different from most standard therapies that typically target just one pathway. In combination with R-ICE (Rituximab, Ifosfamide, Carboplatin, and Etoposide) chemoimmunotherapy, the treatment could potentially enhance effectiveness and offer better outcomes for patients. Additionally, the monotherapy arm provides a less intensive option, which could be beneficial for patients who may not tolerate combination therapies well.

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

Research has shown that combining glofitamab with R-ICE therapy, which participants in Arm A of this trial will receive, may help treat relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Early study results are promising, though they lack detailed specifics. Participants in Arm B will receive glofitamab monotherapy, which helped 46% of patients, with 27% achieving a complete response, meaning their cancer was no longer detectable. However, some patients experienced serious side effects. Both treatment options in this trial have potential, but it's important to weigh the benefits and possible risks. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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 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]

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]

Citations

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Glofitamab in Combination with Rituximab Plus Ifosfamide ... Here, we present preliminary efficacy and safety data for glofitamab in combination with R-ICE (Glofit-R-ICE) in pts with R/R DLBCL eligible for ASCT or CAR T- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05364424

NCT05364424 | A Study Evaluating the Efficacy, Safety, ... The purpose of this study is to evaluate the preliminary efficacy, safety, and pharmacokinetics of glofitamab (glofit) in combination with rituximab plus ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124037340

Glofitamab in Combination with Rituximab Plus Ifosfamide ... Here, we present preliminary efficacy and safety data for glofitamab in combination with R-ICE (Glofit-R-ICE) in pts with R/R DLBCL eligible for ASCT or CAR T- ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/non-hodgkins-lymphoma/a-study-evaluating-the-efficacy--safety--and-pharmacoki-00365.html

Clinical Trial – B-Cell Lymphoma – Efficacy, Safety, and ... A clinical trial to examine the effectiveness and safety of glofitamab in combination with R-ICE (rituximab plus ifosfamide, carboplatin and etoposide)

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A clinical trial to examine the effectiveness and safety of ... The purpose of this study is to evaluate the preliminary efficacy, safety, and pharmacokinetics of glofitamab (glofit) in combination with rituximab plus ...

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Real-world outcomes of patients with aggressive B-cell ... Key PointsBispecifics had an ORR and CR rate of 51.7% and 25.4%, respectively; median PFS and OS were 2.5 and 7.8 months, respectively.

7. 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) after at ...

8. columvi-hcp.com columvi-hcp.com/

COLUMVI™ (glofitamab-gxbm) for third-line or later DLBCL ... Learn how COLUMVI™ (glofitamab-gxbm) is thought to work and about its safety, administration and side effects 3L+ diffuse large B-cell lymphoma, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007195

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) ...

10. 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 ...