Glofitamab + Chemotherapy for Non-Hodgkin's Lymphoma

Recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments—glofitamab (a type of immunotherapy), gemcitabine, and oxaliplatin—on individuals with diffuse large B-cell lymphoma (DLBCL) that has returned or not responded to previous treatments. The researchers aim to determine if this combination can benefit patients who haven't succeeded with standard therapies. The study seeks participants who have tried at least one other treatment, still have measurable cancer, and are not candidates for high-dose chemotherapy with stem cell transplants. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Research has shown that combining glofitamab, gemcitabine, and oxaliplatin to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is promising in terms of safety. Studies have found that glofitamab alone is well-tolerated by patients, even those with extensive prior treatments.

In a study using this combination, the treatment proved effective while keeping side effects manageable. The most common side effects were mild, such as fever and low blood cell counts, which are typical with chemotherapy. Overall, this combination seems to balance effectiveness with safety.

Since the trial is in an early stage, it primarily focuses on assessing the treatment's safety. Researchers closely monitor participants to catch any serious side effects. However, based on current research, the treatment appears generally safe and tolerable for patients with this type of lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of glofitamab with chemotherapy for treating Non-Hodgkin's Lymphoma because it introduces a new mechanism of action. Unlike standard treatments like rituximab, which targets a single protein on cancer cells, glofitamab is a bispecific antibody that can bind to two different proteins, potentially leading to more effective cancer cell destruction. This dual-targeting strategy could improve treatment outcomes by enhancing the immune system’s ability to recognize and kill lymphoma cells. Additionally, the use of glofitamab in combination with gemcitabine and oxaliplatin may provide a more potent therapeutic effect, offering hope for a new and improved approach to managing this type of cancer.

What evidence suggests that this treatment might be an effective treatment for diffuse large B-cell lymphoma?

In this trial, participants will receive a combination of glofitamab, gemcitabine, and oxaliplatin. Research has shown that this combination may be promising for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Specifically, studies have found a 40% improvement in overall survival when patients received this combination compared to other treatments. Additionally, this treatment has demonstrated significant benefits in both overall survival and the time during which the disease does not progress. Early research also indicates that this treatment increases the number and activity of T-cells in tumors, which are crucial for fighting cancer. Overall, these findings suggest that this treatment could be effective for people with this type of lymphoma. ^{1 3 4 5 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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 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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7015

Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx ... With 2 yrs follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS vs R-GemOx in ASCT-ineligible pts with R/R DLBCL.

2. gene.com gene.com/media/press-releases/15070/2025-07-18/genentech-provides-update-on-supplementa

Genentech: Press Releases | Friday, Jul 18, 2025 The sBLA is based on results from the Phase III STARGLO study which showed a statistically significant and clinically meaningful 41% reduction ...

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

New two-year follow-up of Roche's Columvi extends ... Data showed a 40% improvement in overall survival (OS) for patients treated with Columvi® (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) ...

4. ashpublications.org ashpublications.org/blood/article/146/15/1824/546454/Preclinical-advances-in-glofitamab-combinations-a

Preclinical advances in glofitamab combinations: a new ... Glofitamab combination with gemcitabine/oxaliplatin also demonstrated strong efficacy, enhancing intratumor T-cell number, activation, and ...

5. oncologynewscentral.com oncologynewscentral.com/drugs/info/fda-rejects-glofitamab-for-diffuse-large-b-cell-lymphoma-indication

FDA Rejects Glofitamab (Columvi) for Diffuse Large B-cell ... The study evaluated glofitamab plus GemOx versus rituximab plus GemOx in patients with relapsed or refractory DLBCL who had received at least ...

6. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01774-4/abstract

Glofitamab plus gemcitabine and oxaliplatin (GemOx) ... Glofitamab monotherapy induces high complete response rates and manageable safety in Chinese patients with heavily pretreated relapsed or refractory diffuse ...