Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma

Recruiting at 9 trial locations

Overseen By Reference Study ID Number: GO44900 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: Bispecific antibodies, Gemcitabine, Oxaliplatin, Monoclonal antibodies

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had certain cancer treatments like chemotherapy or immunotherapy within 2 weeks before starting the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma?

Research shows that the combination of gemcitabine and oxaliplatin, sometimes with rituximab, has been effective in treating various types of lymphoma, including in patients who have not responded to other treatments. This suggests that the combination of these drugs may be beneficial for Non-Hodgkin's Lymphoma as well. ^{1 2 3 4 5}

Is the combination of Glofitamab and chemotherapy safe for treating Non-Hodgkin's Lymphoma?

Glofitamab, used for treating certain types of Non-Hodgkin's Lymphoma, has shown some safety concerns. In a study, the most common side effect was blood-related issues, and there were a few serious cases, including deaths due to cytokine release syndrome (a severe immune reaction) and febrile neutropenia (fever with low white blood cell count). ^{6 7 8 9 10}

What makes the drug Glofitamab unique for treating non-Hodgkin's lymphoma?

Glofitamab is unique because it is a bispecific antibody that engages T cells to target and destroy cancer cells, specifically designed for patients with relapsed or refractory diffuse large B-cell lymphoma who have limited treatment options. ^{8 9 10 11 12}

What is the purpose of this trial?

The purpose of the study is to evaluate glofitamab + gemcitabine + oxaliplatin in participants in the United States, including under-represented racial and ethnic populations, that have relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for U.S. patients with Diffuse Large B-Cell Lymphoma (DLBCL) that has come back or didn't respond to treatment. They must have only failed one therapy and not be candidates for high-dose chemo and stem cell transplant, have measurable cancer on scans, had at least one systemic therapy, and be in a stable enough condition to participate (ECOG 0-2).

Inclusion Criteria

I have had one treatment for my condition and cannot have high-dose chemo with a stem cell transplant.

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

I have received at least one treatment for my condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of intravenous obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin, and then up to 4 cycles of glofitamab monotherapy

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• Glofitamab
• Oxaliplatin

Trial Overview The study tests the combination of Glofitamab with Gemcitabine and Oxaliplatin in participants, focusing also on including diverse racial and ethnic groups. It aims to see how safe this combo is and how well it works against relapsed or refractory DLBCL.

Participant Groups

Group I: Gemcitabine + Glofitamab + Oxaliplatin Experimental Treatment 5 Interventions

Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung 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

In a Phase I trial involving 10 patients with intermediate grade non-Hodgkin lymphoma (NHL), the combination of gemcitabine at 500 mg/m² with standard CHOP chemotherapy was found to be the maximum tolerated dose, showing a 71% survival rate at 2.5 years.

The study reported significant toxicities, particularly in the higher dose cohort (750 mg/m²), where three out of four patients experienced dose-limiting toxicities, highlighting the need for careful monitoring and potential dose adjustments in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL. Reagan, JL., Rosmarin, A., Butera, JN., et al.[2022]

In a phase 2 clinical trial involving 60 elderly patients with untreated diffuse large B-cell lymphoma, the R-GemOx regimen (rituximab, gemcitabine, and oxaliplatin) demonstrated high efficacy, with 75% of patients achieving an overall response and 47% achieving a complete response.

The treatment was well-tolerated, with no treatment-related deaths reported, although some patients experienced grade 3-4 adverse events, primarily hematological toxicities, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial. Shen, QD., Zhu, HY., Wang, L., et al.[2022]

In a study of 62 patients with relapsed/refractory B-cell lymphoma, the combination of gemcitabine and oxaliplatin (GEMOX) showed an overall response rate of 57%, while adding rituximab (R-GEMOX) improved the response rate to 78%.

R-GEMOX demonstrated better failure-free survival (28% at 42 months) and overall survival (37% at 42 months) compared to GEMOX, indicating that the addition of rituximab enhances treatment efficacy, although both treatments had significant side effects like neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Corazzelli, G., Capobianco, G., Arcamone, M., et al.[2022]

The GIDOX treatment regimen showed a 52% overall response rate in 27 patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, with 15% achieving complete remission and 37% partial remission after three cycles.

Despite some significant toxicities, including grade 3 and 4 neutropenia and thrombocytopenia, GIDOX was generally well-tolerated, allowing 26% of patients to proceed to high-dose chemotherapy followed by autologous stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin's lymphoma: a consortium for improving survival of lymphoma (CISL) trial. Park, BB., Kim, WS., Eom, HS., et al.[2022]

The GEMOX regimen, combining gemcitabine and oxaliplatin, showed an overall response rate of 45.8% in 24 lymphoma patients who had previously failed multiple chemotherapy treatments, with some achieving long-term survival.

While the treatment was effective, it was associated with significant hematologic toxicity, including grade III or IV neutropenia in 59.3% of patients, indicating that while GEMOX can be beneficial, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens]. Yang, J., Shi, Y., He, X., et al.[2014]

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]

In a study of 56 patients with relapsed/refractory follicular lymphoma, obinutuzumab combined with chemotherapy (either G-CHOP or G-FC) resulted in high response rates of 93% to 96%, indicating strong efficacy for this treatment approach.

The safety profile was acceptable, with most adverse events being mild infusion-related reactions; however, G-FC was associated with more adverse events compared to G-CHOP, suggesting that while both regimens are effective, G-CHOP may be better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Radford, J., Davies, A., Cartron, G., 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 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]

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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial examining addition of gemcitabine to CHOP in intermediate grade NHL. [2022]

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

Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. [2022]

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

Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin's lymphoma: a consortium for improving survival of lymphoma (CISL) trial. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens]. [2014]

6. 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]

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

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]

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

Glofitamab: First Approval. [2023]

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

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

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

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

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

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