Glofitamab Combo vs Rituximab Combo for Diffuse Large B-Cell Lymphoma

Recruiting at 103 trial locations

Overseen By Reference Study ID Number: GO41944 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS disease, Active infection, Autoimmune, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

270 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for patients with a type of lymphoma that has come back or didn't respond to previous treatments. The treatment combines glofitamab, which helps the immune system attack cancer, with two chemotherapy drugs that kill cancer cells.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had chemotherapy, immunotherapy, or certain other treatments within 2 to 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug Rituximab in treating diffuse large B-cell lymphoma?

Rituximab, when combined with chemotherapy, has been shown to improve survival and tumor remission in patients with diffuse large B-cell lymphoma, making it a valuable option for treatment. ^{1 2 3 4 5}

Is the Glofitamab Combo vs Rituximab Combo treatment generally safe for humans?

The combination of rituximab with chemotherapy, including gemcitabine and oxaliplatin, has shown a low toxicity profile in elderly patients with diffuse large B-cell lymphoma. Additionally, rituximab combined with CHOP chemotherapy has been found to have similar safety profiles, with manageable side effects compared to CHOP alone. ^{6 7 8 9 10}

What makes the Glofitamab Combo treatment unique for diffuse large B-cell lymphoma?

The Glofitamab Combo treatment is unique because it includes glofitamab, a bispecific antibody that targets both CD20 and CD3, engaging T-cells to attack the cancer cells. This mechanism is different from traditional treatments and offers a novel approach for patients who have relapsed or are refractory to other therapies. ^{5 11 12 13 14}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with relapsed/refractory diffuse large B-cell lymphoma who have had at least one prior systemic therapy and are not candidates for stem cell transplant. Participants must have measurable disease, be in stable condition (ECOG 0-2), have adequate organ function, and a recent negative COVID-19 test.

Inclusion Criteria

My disease came back or didn't respond to treatment within 6 months of my last therapy.

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

My diagnosis is diffuse large B-cell lymphoma.

Exclusion Criteria

I have or might have a long-term Epstein-Barr virus infection.

My condition is primary mediastinal B-cell lymphoma.

I cannot take obinutuzumab, rituximab, gemcitabine, oxaliplatin, or tocilizumab due to adverse reactions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Glofit-GemOx or R-GemOx for up to 8 cycles, with each cycle lasting 21 days

24 weeks

Monotherapy

Participants in the Glofit-GemOx arm receive up to 4 additional cycles of glofitamab monotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Gemcitabine
• Glofitamab
• Oxaliplatin
• Rituximab

Trial Overview The study compares the effectiveness of two treatments: Glofitamab combined with Gemcitabine + Oxaliplatin versus Rituximab with the same chemotherapy drugs. It aims to determine which combination is more effective for patients who haven't responded well to previous therapies.

Participant Groups

Group I: R-GemOx Experimental Treatment 3 Interventions

Participants will receive rituxumab (R) in combination with gemcitabine and oxaliplatin (GemOx) for up to 8 cycles. Treatment is administered in 21-day cycles.

Group II: Glofit-GemOx Experimental Treatment 5 Interventions

Participants will receive up to 8 cycles of glofitamab (Glofit) in combination with gemcitabine and oxaliplatin (GemOx), followed by up to 4 cycles of glofitamab monotherapy. A single dose of obinutuzumab will be administered 7 days prior to the first dose of glofitamab. Treatment is administered in 21-day cycles.

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

Rituximab, an anti-CD20 monoclonal antibody, significantly improves treatment outcomes for patients with indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL) when used in combination with chemotherapy, leading to better tumor remission and patient survival compared to chemotherapy alone.

Rituximab maintenance therapy prolongs tumor remission and is generally well tolerated, making it a valuable option for both first- and second-line treatments in advanced-stage B-cell NHL and CLL, and it is included in current treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Cvetković, RS., Perry, CM.[2018]

Rituximab, an anti-CD20 monoclonal antibody, significantly improves tumor remission and patient survival when used in combination with chemotherapy for patients with B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), based on phase III trials.

The drug is generally well tolerated and has been shown to prolong remission when used as maintenance therapy, making it a valuable treatment option included in current guidelines for advanced-stage B-cell NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Cvetković, RS., Perry, CM.[2018]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

Rituximab, when added to standard chemotherapy, significantly improved survival rates in patients with non-Hodgkin's lymphoma.

In patients with chronic B-cell lymphocytic leukemia, the addition of rituximab to fludarabine-based regimens enhanced both response rates and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety and feasibility of rapid infusion of rituximab. Atmar, J.[2022]

In a study involving four patients with primary refractory or early relapsed T cell rich B cell lymphomas (TCRBCL), the combination of rituximab with chemotherapy (vinorelbine and gemcitabine) resulted in three complete responses and one partial response, demonstrating significant efficacy.

The treatment was well-tolerated, with no significant adverse effects reported, suggesting that rituximab combined with chemotherapy could be a promising option for treating TCRBCL and warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study. Xiros, N., Economopoulos, T., Valsami, S., 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]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

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]

In a study of 34 patients with relapsed/refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), maintenance therapy with lenalidomide after bendamustine and rituximab (BR) did not significantly improve progression-free survival (PFS), which was 18.3 months compared to 15.2 months without maintenance.

The study highlighted challenges with lenalidomide maintenance due to hematological and infectious toxicities, as only 6 out of 19 patients completed the intended 12 cycles, suggesting that lenalidomide may be more effective in earlier treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study. Chang, JE., Havighurst, T., Kim, K., et al.[2018]

References

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

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. [2018]

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

Spotlight on rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. [2018]

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

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. [2017]

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

Review of the safety and feasibility of rapid infusion of rituximab. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study. [2022]

6. 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]

7. Japan pubmed.ncbi.nlm.nih.gov

Phase II study of CHOP-GR therapy in diffuse large B-cell lymphoma. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Comparison between efficacy and safety of rituximab plus CHOP regimen and CHOP regimen for treatment of newly diagnosed patients with diffuse large B-cell lymphoma]. [2016]

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

Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

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

Glofitamab: First Approval. [2023]

12. England pubmed.ncbi.nlm.nih.gov

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

13. 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]

14. England pubmed.ncbi.nlm.nih.gov

Bendamustine + rituximab chemoimmunotherapy and maintenance lenalidomide in relapsed, refractory chronic lymphocytic leukaemia and small lymphocytic lymphoma: A Wisconsin Oncology Network Study. [2018]