Glofitamab + Obinutuzumab for Non-Hodgkin's Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Celeste Carey

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Reid Merryman, MD

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, 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: 6

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two immunotherapy drugs, glofitamab and obinutuzumab, in treating Non-Hodgkin's Lymphomas, specifically Follicular Lymphoma and Marginal Zone Lymphoma. Researchers aim to determine if this drug combination is effective and safe for patients who have not received other treatments for their lymphoma. It suits those diagnosed with these lymphoma types and experiencing symptoms like swollen lymph nodes or organ issues due to the disease. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people, offering patients a chance to contribute to significant advancements in lymphoma care.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic immunosuppressive therapy or high doses of corticosteroids. If you are on a short course of steroids, you should be off them at least 7 days before starting the trial.

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

Research has shown that the combination of glofitamab and obinutuzumab has been studied for safety in various situations. In other types of lymphoma, more than half of the patients taking glofitamab experienced serious side effects, indicating strong reactions to the treatment for some individuals.

Obinutuzumab is already approved for treating certain blood cancers, suggesting it is generally considered safe for those conditions, although side effects can still occur.

The current trial is in Phase 2, aiming to gather more information on the treatments' safety and effectiveness. Previous studies suggest that while these treatments can have strong effects, their safety is being closely monitored. Prospective participants should consider the potential benefits and risks and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Glofitamab and Obinutuzumab for treating Non-Hodgkin's Lymphoma, particularly because these treatments work differently than existing options. Most current therapies target cancer cells broadly, but Glofitamab is a bispecific antibody that specifically links cancer cells with immune cells, prompting a more precise immune response against the lymphoma. Obinutuzumab, meanwhile, is an engineered antibody that targets a specific protein on the surface of B-cells, which are often involved in these lymphomas, leading to their destruction. Together, these treatments offer a targeted approach that could be more effective and potentially less toxic compared to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

This trial will evaluate the combination of two treatments, glofitamab and obinutuzumab, for follicular lymphoma (FL) and marginal zone lymphoma (MZL). Glofitamab helps the body's immune cells, called T-cells, attack cancer cells. Studies have found that it works in about 52% of certain lymphoma cases. Obinutuzumab boosts the immune system's ability to fight cancer. Together, these treatments might shrink tumors and slow the disease. Although more research is needed, early results are promising for people with FL and MZL. ^{1 6 7 8 9}

Who Is on the Research Team?

Reid W Merryman, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with Follicular Lymphoma or Marginal Zone Lymphoma who haven't had systemic therapy for these conditions. They should have adequate organ function, no urgent need for chemotherapy, and agree to use effective contraception. Excluded are those with recent major surgery, uncontrolled infections, certain heart conditions, severe allergies to monoclonal antibodies, autoimmune diseases without clearance, prior transplants or immunosuppressive therapy needs.

Inclusion Criteria

I haven't had systemic therapy for my lymphoma, but I may have had radiation or steroids.

My lymphoma is confirmed as FL (grade 1-3A) or MZL, without active transformation.

Adequate hematologic and organ function: Absolute neutrophil count, Platelets, Creatinine clearance, Total bilirubin, AST/ALT, Ability to understand and the willingness to sign a written informed consent document, Willingness to provide a pre-treatment tumor sample by core needle or excisional surgical biopsy, Willingness to remain abstinent or to use two effective contraceptive methods.

Exclusion Criteria

I have had a solid organ or bone marrow transplant.

I do not have any severe or uncontrolled medical conditions.

I haven't had any live vaccines in the week before or during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Obinutuzumab and Glofitamab for approximately 9 months

9 months

Multiple visits (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits (in-person) up to 5 years

Long-term follow-up

Participants are monitored for long-term outcomes and survival

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Obinutuzumab

Trial Overview

The trial is testing the effectiveness and safety of combining two immunotherapy drugs: Glofitamab and Obinutuzumab in treating patients with Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL). It's aimed at those who haven't received previous treatments for their lymphoma.

How Is the Trial Designed?

Group I: Obinutuzumab + Glofitamab for Marginal Zone Lymphoma Experimental Treatment 2 Interventions

Participants will undergo study procedures as outlined: * Imaging scans (CT or PET) at screening and after cycles 3, 7, and 12 of treatment. * Bone marrow biopsy at baseline. * Cycle 1 * Days -21, -14, -7, 0 of 36 day cycle: Predetermined dose of Obinutuzumab. * Days 1 and 8 of 36 day cycle: Predetermined dose of Glofitamab. (First dose will be administered in the hospital.) * Cycles 2 - 12: o Day 1 of 21 day cycle: Predetermined dose of Glofitamab. * Bone marrow biopsy within 2 weeks of end of treatment. * Imaging scans (CT or PET) at 12, 18, and 24 months after treatment initiation. * Follow up visits up to 5 years after treatment completion.

Group II: Obinutuzumab + Glofitamab for Follicular Lymphoma Experimental Treatment 2 Interventions

Participants will undergo study procedures as outlined: * Imaging scans (CT or PET) at screening and after cycles 3, 7, and 12 of treatment. * Bone marrow biopsy at baseline. * Cycle 1 * Days -21, -14, -7, 0 of 36 day cycle: Predetermined dose of Obinutuzumab. * Days 1 and 8 of 36 day cycle: Predetermined dose of Glofitamab. (First dose will be administered in the hospital.) * Cycles 2 - 12: o Day 1 of 21 day cycle: Predetermined dose of Glofitamab. * Bone marrow biopsy within 2 weeks of end of treatment. * Imaging scans (CT or PET) at 12, 18, and 24 months after treatment initiation. * Follow up visits up to 5 years after treatment completion.

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?

Reid Merryman, MD

Lead Sponsor

Trials

3

Recruited

110+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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]

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]

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 is an effective treatment for B-cell malignancies, specifically approved in the US for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, showcasing its efficacy in targeting cancer cells.

Utilizing GlycoMAb® technology, obinutuzumab enhances immune-mediated cell death through increased antibody-dependent cellular cytotoxicity, making it a promising option in ongoing phase III trials for various B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. Cameron, F., McCormack, PL.[2021]

Obinutuzumab, a novel CD20 antibody, demonstrated superior anti-tumor activity compared to rituximab in preclinical mouse models of non-Hodgkin lymphoma, particularly when combined with chemotherapy agents like bendamustine.

In these studies, obinutuzumab alone was at least as effective as rituximab combined with chemotherapy, suggesting it could be a more effective treatment option for patients with non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma. Herting, F., Friess, T., Bader, S., 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]

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]

Obinutuzumab combined with bendamustine (G+B) significantly improves progression-free survival and overall survival in patients with follicular lymphoma who have relapsed after rituximab treatment, compared to bendamustine alone.

The cost-effectiveness analysis indicates that G+B is likely a cost-effective treatment option, with an incremental cost-effectiveness ratio of $47,000 per quality-adjusted life year (QALY) gained, showing a 98% probability of being cost-effective at the $100,000 per QALY threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US. Guzauskas, GF., Masaquel, A., Reyes, C., et al.[2019]

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

In the phase III GALLIUM trial involving 1202 patients with previously untreated follicular lymphoma, obinutuzumab-based immunochemotherapy significantly improved progression-free survival (PFS) compared to rituximab-based therapy, with 7-year PFS rates of 63.4% versus 55.7%.

While both treatments had similar overall survival rates (88.5% for obinutuzumab vs. 87.2% for rituximab), serious adverse events were reported in about 49% of patients receiving obinutuzumab and 43% for rituximab, indicating comparable safety profiles without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. Townsend, W., Hiddemann, W., Buske, C., et al.[2023]

The Phase III GADOLIN trial showed that obinutuzumab combined with bendamustine significantly improves progression-free survival in patients with rituximab-refractory indolent non-Hodgkin lymphoma compared to bendamustine alone.

Obinutuzumab has received FDA approval for treating follicular lymphoma that has relapsed or is refractory to rituximab, highlighting its efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab for the treatment of indolent lymphoma. Edelmann, J., Gribben, JG.[2018]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05783596

NCT05783596 | Glofit and Obin in Follicular Lymphoma ...

The purpose of this study is to determine how effective and safe the combination of glofitamab and obinutuzumab is in treating patients with Follicular ...

2.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05779

Glofitamab and Obinutuzumab for the Treatment of Patients ...

Combination therapy with glofitamab and obinutuzumab may be effective in treating patients with follicular lymphoma or marginal zone lymphoma. Additionally ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ...

Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

4.

dana-farber.org

dana-farber.org/clinical-trials/22-632

A Phase 2 Study of Glofitamab and Obinutuzumab for first- ...

The purpose of this study is to determine how effective and safe the combination of glofitamab and obinutuzumab is in treating patients with Follicular ...

5.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2023/761309Orig1s000MultidisciplineR.pdf

761309Orig1s000 - accessdata.fda.gov

cell lymphoma, additional data would be helpful to further evaluate glofitamab in these populations. Refer to Section 12 for the resultant PMC. 7.1.2.6 ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03075696

NCT03075696 | A Dose Escalation Study of Glofitamab ...

This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a ...

7.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2206913

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell ...

Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

8.

ashpublications.org

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

Preclinical advances in glofitamab combinations: a new ...

Glofitamab combinations with chemotherapy and antibody-drug conjugates reveal strong synergy in preclinical humanized lymphoma models.

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK604438/

Clinical Review - Glofitamab (Columvi) - NCBI - NIH

The experts highlighted that glofitamab should be restricted to patients who are not eligible for other curative therapies, patients who have already received ...