Glofitamab + Gemcitabine + Oxaliplatin for Lymphoma

Recruiting at 53 trial locations

Overseen By Reference Study ID Number: GO45434 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Monoclonal antibodies, Immunosuppressive drugs

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

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the frequency and severity of cytokine release syndrome (CRS) in people with diffuse large B-cell lymphoma (DLBCL). It tests a combination of medications: glofitamab (a type of immunotherapy), gemcitabine, and oxaliplatin, followed by glofitamab alone. People with DLBCL whose disease has returned or worsened after prior treatments and who are not candidates for high-dose chemotherapy and stem cell transplant might be suitable participants. The study aims to understand the treatment's impact and potential side effects to improve future therapies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in DLBCL therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain cancer treatments, like chemotherapy or immunotherapy, within 2 weeks before starting the study, and you should not be on systemic immunosuppressive medications within 4 weeks prior to the first dose.

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

Research has shown that the combination of glofitamab, gemcitabine, and oxaliplatin is generally well-tolerated by patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (R/R DLBCL). This treatment, known as Glofit-GemOx, has significantly improved survival compared to some existing treatments.

Regarding safety, studies have shown positive results, but side effects can occur. One concern with glofitamab is cytokine release syndrome (CRS), a reaction that can occur when the immune system becomes very active. The trial aims to determine the frequency and severity of CRS with this treatment combination.

Overall, current evidence suggests that Glofit-GemOx is promising in terms of both effectiveness and safety, but participants should be aware of possible side effects like CRS. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining glofitamab, gemcitabine, and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) because it offers a novel approach compared to standard therapies like R-CHOP. Unlike typical regimens that often rely on broad-acting chemotherapy agents, this combination includes glofitamab, a bispecific antibody that uniquely targets CD20 and CD3, potentially enhancing the immune system's ability to attack cancer cells. Additionally, the use of glofitamab monotherapy after the initial treatment rounds could maintain remission and improve long-term outcomes. This targeted mechanism and strategic combination could offer a more effective and sustained response for patients who have limited options.

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

Research has shown that the combination of three drugs—glofitamab, gemcitabine, and oxaliplatin—may be promising for treating diffuse large B-cell lymphoma (DLBCL). Earlier studies demonstrated that this combination, known as Glofit-GemOx, significantly improved overall survival compared to other treatments. Specifically, patients who received this therapy had a 40% higher survival rate. In this trial, participants with relapsed or refractory DLBCL will receive obinutuzumab pre-treatment, followed by the Glofit-GemOx combination, and then glofitamab monotherapy. This suggests that Glofit-GemOx could be a viable option for those with relapsed or hard-to-treat DLBCL who cannot undergo a stem cell transplant. The evidence supports its potential to extend survival for patients with this type of lymphoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least one systemic therapy and are not candidates for stem cell transplant. They should be relatively active (ECOG status 0, 1, or 2), have measurable cancer lesions, and good blood and kidney function. Exclusions include severe allergies to monoclonal antibodies, prior treatments with certain drugs listed, significant other diseases or conditions that could interfere with the study or pose risks.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

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

I have received at least one treatment for my condition.

Exclusion Criteria

My slow-growing cancer has changed into aggressive large B-cell lymphoma.

Prior enrollment in Study GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085)

My condition is primary mediastinal B-cell lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, and then glofitamab monotherapy

12 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 trial tests how often and how severely patients experience cytokine release syndrome when treated with a combination of glofitamab + gemcitabine + oxaliplatin followed by only glofitamab. It aims to optimize this treatment regimen's safety profile in those with relapsed/refractory DLBCL.

How Is the Trial Designed?

Group I: R/R DLBCL Experimental Treatment 4 Interventions

Participants with R/R DLBCL will receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, followed by glofitamab monotherapy.

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

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]

The addition of immune checkpoint inhibitors to chemotherapy does not significantly increase the risk of high-grade hematological toxicities like anemia, thrombocytopenia, or neutropenia, based on a meta-analysis of 11 studies.

However, the combination treatment does lead to a significantly higher risk of high-grade diarrhea, indicating a specific area of concern for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity patterns associated with chemotherapy/immune checkpoint inhibitor combinations: a meta-analysis. Abdel-Rahman, O.[2020]

Immune checkpoint inhibitor (ICI) combination therapy significantly improves objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) in patients with advanced malignancies, based on a meta-analysis of 10 studies involving 2410 patients.

While ICI combination therapy shows enhanced efficacy compared to monotherapy, it is associated with a higher incidence of severe adverse events, including fatigue, nausea, and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review. Ma, X., Zhang, Y., Wang, S., et al.[2021]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

A patient with NK/T-cell lymphoma developed toxic epidermal necrolysis (TEN) after receiving a combination of sintilimab and P-GemOx chemotherapy, highlighting a serious risk associated with this treatment regimen.

This case emphasizes the need for careful monitoring of skin-related toxicities when using PD-1 inhibitors like sintilimab in combination with other chemotherapy agents, as TEN can occur rapidly and may be life-threatening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis associated with chemoimmunotherapy for lymphoma: case report and literature review. Yang, W., Xu, X., Xia, D., et al.[2022]

In a meta-analysis of 18 studies involving 5,649 patients with non-small cell lung cancer, first-line therapy using PD-1/PD-L1 inhibitors showed a significantly higher risk of treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) compared to subsequent therapies, indicating a need for careful monitoring in initial treatments.

Despite the higher incidence of adverse events in first-line therapy, the types of trAEs and irAEs were largely similar across different therapy lines, suggesting that while the severity may differ, the overall spectrum of side effects remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. Yang, Y., Pang, P., Xie, Z., et al.[2022]

The combination of gemcitabine, dexamethasone, and cisplatin (GDP) showed a promising overall response rate of 49% in patients with recurrent or refractory non-Hodgkin lymphoma, with 16% achieving complete responses after two treatment cycles.

Despite some significant toxicities, such as grade 3 and 4 neutropenia in 33% and 39% of patients respectively, the GDP regimen can be safely administered to outpatients, allowing many patients to proceed to stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Crump, M., Baetz, T., Couban, S., et al.[2022]

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 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 44 patients with relapsed aggressive lymphoma, the Gemcitabine/Oxaliplatin (Gem-Ox) regimen, with or without rituximab, showed an overall response rate of 43% and a complete response rate of 30%, indicating its efficacy as a second-line treatment.

Despite its favorable toxicity profile compared to more aggressive inpatient regimens, the treatment was associated with significant hematological toxicity, including a 22% incidence of febrile neutropenia, and the median overall survival for patients remained low at 8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome for patients with relapsed/refractory aggressive lymphoma treated with gemcitabine and oxaliplatin with or without rituximab; a retrospective, multicentre study. Dhanapal, V., Gunasekara, M., Lianwea, C., 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39550172/

Glofitamab plus gemcitabine and oxaliplatin (GemOx) ... Glofit-GemOx had a significant overall survival benefit compared with R-GemOx, supporting its use in transplant-ineligible patients with relapsed or refractory ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5027/533645/Glofitamab-with-Gemcitabine-and-Oxaliplatin-Is

Glofitamab with Gemcitabine and Oxaliplatin Is Cost-Effective ... The aim of this analysis was to investigate the cost-effectiveness of Glofit-GemOx vs R-GemOx in patients with ASCT-ineligible R/R DLBCL, from a United States ...

4. 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) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06806033

NCT06806033 | A Study to Evaluate the Optimization of ... Participants with R/R DLBCL will receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, followed by glofitamab monotherapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06624085

NCT06624085 | A Study Evaluating the Safety and Efficacy ... The purpose of the study is to evaluate glofitamab + gemcitabine + oxaliplatin in participants in the United States, including under-represented racial and ...

7. ashpublications.org ashpublications.org/ashclinicalnews/news/8601/Glofitamab-Plus-GemOx-Combination-Completely

Glofitamab Plus GemOx Combination 'Completely Practice ... The glofitamab plus GemOx combination will be completely practice changing when the FDA approves it,” Dr. Brody said.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025022761

ABCL-544: Glofitamab Plus Gemcitabine and Oxaliplatin ... Present updated efficacy and safety data from STARGLO for Glofit-GemOx vs rituximab combined with GemOx (R-GemOx) in patients with R/R DLBCL. Methods.