Glofitamab + Obinutuzumab for Non-Hodgkin's Lymphoma

Recruiting at 61 trial locations

Overseen By Reference Study ID Number: NP30179 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

920 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests glofitamab, a new drug given through an IV that helps immune cells attack cancer cells. It targets patients who need new treatment options because their cancer hasn't responded to existing treatments. The drug works by connecting immune cells to cancer cells, making it easier for the immune system to destroy the cancer. Glofitamab shows promise in treating certain types of blood cancers.

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 received certain treatments like systemic immunotherapeutic agents or standard chemotherapy within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before starting the study. Specifically, you must not have taken systemic immunotherapeutic agents, standard chemotherapy, or other investigational anti-cancer agents within 4 weeks prior to the study. Additionally, you should not have received systemic immunosuppressive medications within two weeks before the study, except for low-dose corticosteroids.

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

Obinutuzumab, a part of the treatment, has shown improved effectiveness over rituximab in treating follicular lymphoma, a type of Non-Hodgkin's Lymphoma, especially in patients who are resistant to rituximab. It has been approved for use in combination with chemotherapy for certain lymphoma patients, indicating its potential effectiveness. ^{1 2 3 4 5}

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

Research shows that Obinutuzumab, a part of this drug combination, has improved outcomes in follicular lymphoma, a type of Non-Hodgkin's Lymphoma, especially in patients who did not respond to the standard treatment, Rituximab. It has been shown to be more effective than Rituximab in some cases, suggesting potential benefits for similar conditions. ^{1 2 3 4 5}

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

Glofitamab and Obinutuzumab have been studied for safety in treating Non-Hodgkin's Lymphoma. Common side effects include infusion-related reactions (mild to moderate reactions during or after the drug is given) and hematological toxicity (blood-related side effects). Serious side effects, such as cytokine release syndrome (a severe immune reaction) and febrile neutropenia (fever with low white blood cell count), have been reported, but these are less common. ^{6 7 8 9 10}

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

Glofitamab and Obinutuzumab have been studied for safety in treating Non-Hodgkin's Lymphoma. Common side effects include infusion-related reactions (mild to moderate reactions during or after the drug is given) and hematological toxicity (blood-related side effects). Serious side effects, like cytokine release syndrome (a severe immune reaction) and febrile neutropenia (fever with low white blood cell count), have been reported, but they are less common. ^{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 simultaneously targets CD20 on B-cells and CD3 on T-cells, helping the immune system directly attack cancer cells. Its novel 2:1 structure enhances its ability to bind to CD20, potentially leading to more effective treatment outcomes for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. ^{6 7 9 10 11}

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

Glofitamab is unique because it is a bispecific antibody that simultaneously targets CD20 on B-cells and CD3 on T-cells, helping the immune system to directly attack cancer cells. Its novel 2:1 structure enhances its binding to CD20, potentially leading to more effective treatment outcomes for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma who have limited options. ^{6 7 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with relapsed/refractory B-Cell Non-Hodgkin's Lymphoma who've had at least one prior treatment and lack other survival-prolonging options. Participants must have measurable disease, be in good physical condition (ECOG 0 or 1), and have proper liver, kidney, and blood function. Pregnant women are excluded, as well as those with certain infections or a history of severe reactions to similar drugs.

Inclusion Criteria

Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential

I have no treatment options left that could extend my life.

I can provide a fresh biopsy from a site that is safe to access, as long as I have more than one measurable lesion.

Exclusion Criteria

I haven't had cancer treatment in the last 4 weeks.

I haven't taken any immune-weakening drugs in the last two weeks.

I don't have an ongoing infection confirmed by a test or doctor's opinion.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive obinutuzumab pretreatment followed by glofitamab IV infusion with ascending doses to determine MTD/OBD

24 weeks

Bi-weekly visits for 12 cycles

Dose Expansion

Participants receive glofitamab at a fixed or step-up dose regimen to further evaluate safety and therapeutic activity

12 cycles

Every 2 or 3 weeks as determined in Part II

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Glofitamab
• Obinutuzumab
• Tocilizumab

Trial Overview The study tests Glofitamab alone or combined with Obinutuzumab in patients pre-treated with a fixed dose of Obinutuzumab. It's an early-phase trial to find the safest and most effective doses (Phase I/II). The trial includes escalating doses followed by expansion cohorts once optimal dosing is determined.

Participant Groups

Group I: Part III: Dose Expansion Experimental Treatment 3 Interventions

Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7, followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.

Group II: Part II: Dose Escalation Experimental Treatment 3 Interventions

In each treatment regimen, participants will receive Gpt 1000 mg IV infusion on Day -7; or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of Q2W or every 3 week (Q3W) cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of Q3W cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on Cycle 1 Day 1, followed by a higher dose on Cycle 1 Day 8; the total dose in Cycle 1 will not exceed the previously determined MTD. Higher doses may be explored from Cycle 2 or later cycles.

Group III: Part I: Dose Escalation Experimental Treatment 3 Interventions

Participants (single participant cohorts) will receive obinutuzumab pretreatment (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week (Q2W) cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.

Glofitamab is already approved in United States for the following indications:

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

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 the GALLIUM trial involving patients with front-line follicular lymphoma, obinutuzumab (G) exposure was found to be lower in males and patients with higher body weight, but this variability did not affect progression-free survival (PFS) in those treated with G plus bendamustine.

For patients receiving G with CHOP or CVP chemotherapy, higher average drug concentration (CmeanIND) was associated with improved PFS, suggesting that drug exposure may play a role in treatment efficacy for these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first-line immunochemotherapy. Jamois, C., Gibiansky, E., Gibiansky, L., et al.[2021]

Obinutuzumab (G) combined with chemotherapy (G + Chemo) is shown to be a cost-effective treatment for previously untreated follicular lymphoma (FL) in Japan, with incremental cost-effectiveness ratios (ICERs) below the acceptable threshold of 7.5 million JPY per quality-adjusted life year (QALY).

The study found that the lowest lifetime direct medical costs were associated with the R-bendamustine (R-B) treatment group, primarily due to reduced hospitalization costs, highlighting the impact of treatment settings on overall expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. Ohno, S., Shoji, A., Hatake, K., et al.[2021]

Obinutuzumab, a new anti-CD20 monoclonal antibody, has shown promising efficacy in treating follicular lymphoma (FL) and has been approved by the FDA for use in combination with bendamustine for patients who have relapsed after rituximab treatment.

Ongoing phase III trials, such as the GALLIUM trial, suggest that obinutuzumab may soon be established as a first-line treatment for FL, potentially replacing rituximab as the gold standard, although some safety concerns remain to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab in follicular lymphoma. Martinez-Calle, N., Figueroa-Mora, R., Villar-Fernandez, S., et al.[2017]

Obinutuzumab, a novel anti-CD20 monoclonal antibody, shows improved efficacy over rituximab in treating patients with rituximab-relapsed/refractory follicular lymphoma, as demonstrated through an analysis of data from 6 clinical trials involving patients with CD20+ B-cell malignancies.

The pharmacokinetic model indicates that while higher exposure to obinutuzumab is associated with greater efficacy, particularly in terms of longer progression-free survival, the clinical benefits of the treatment are achieved regardless of exposure variability, ensuring safety and minimizing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Gibiansky, E., Gibiansky, L., Buchheit, V., et al.[2021]

In a study of 143 treatment-naïve patients with follicular lymphoma, obinutuzumab-based induction regimens showed high effectiveness, with a complete response rate of 69.9% and a partial response rate of 26.5%.

Infusion-related reactions were infrequent, occurring in only 9.1% of patients during the first administration of obinutuzumab, regardless of whether the total dose was given in one day or split over two days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group. Paszkiewicz-Kozik, E., Hus, I., Palka, M., 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]

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 is a novel bispecific T-cell recruiting antibody that targets both CD20 on B-cells and CD3 on T-cells, showing over 50% complete response rates in heavily treated patients with aggressive and indolent B-cell lymphoma during Phase 1 trials.

The unique 2:1 configuration of glofitamab allows for an extended half-life and superior binding to CD20, making it a promising option for patients with limited treatment choices, with ongoing trials evaluating its efficacy in combination therapies and earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. Minson, A., Dickinson, M.[2022]

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 targeting CD20 and CD3, demonstrated clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma during a phase 1 trial, showing T-cell activation and tumor cell killing.

The study identified that tumor intrinsic factors, such as TP53 signaling, may contribute to resistance against glofitamab, indicating that these factors could serve as important biomarkers for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Bröske, AE., Korfi, K., Belousov, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first-line immunochemotherapy. [2021]

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

Cost-effectiveness analysis of treatment regimens with obinutuzumab plus chemotherapy in Japan for untreated follicular lymphoma patients. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

Obinutuzumab in follicular lymphoma. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. [2021]

5. Poland pubmed.ncbi.nlm.nih.gov

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group. [2023]

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

Glofitamab: First Approval. [2023]

7. 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]

8. 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]

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

Glofitamab CD20-TCB bispecific antibody. [2022]

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

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

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

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. [2022]