Glofitamab + Obinutuzumab for Non-Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Reid W Merryman, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Reid Merryman, MD

Must not be taking: Immunosuppressants, Corticosteroids

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine how effective and safe the combination of glofitamab and obinutuzumab is in treating patients with Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL) who have not received other treatments for their lymphoma. The names of the study drugs involved in this study are: * Glofitamab (a type of immunotherapy) * Obinutuzumab (a type of immunotherapy)

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.

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

Research shows that Obinutuzumab, when used with chemotherapy, has been effective in treating follicular lymphoma, a type of Non-Hodgkin's Lymphoma, especially in patients who did not respond to previous treatments. It has been shown to improve survival rates and reduce tumor growth compared to other treatments. ^{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. Glofitamab, when used with Obinutuzumab pretreatment, showed manageable safety with some infusion-related reactions. Obinutuzumab has a generally manageable safety profile, with mild to moderate infusion-related reactions and neutropenia (low white blood cell count) being common side effects. ^{1 6 7 8 9}

What makes the drug Glofitamab + Obinutuzumab unique for treating Non-Hodgkin's Lymphoma?

The combination of Glofitamab and Obinutuzumab is unique because it uses two monoclonal antibodies that target CD20, a protein on the surface of B-cells, enhancing the immune system's ability to attack cancer cells. Obinutuzumab is a newer generation antibody that has been engineered to improve its effectiveness compared to older treatments like Rituximab, potentially offering better outcomes for patients who have relapsed or are resistant to previous therapies. ^{1 2 3 10 11}

Research Team

Reid W Merryman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Meets at least one criterion to begin treatment based on the modified GELF criteria: Symptomatic adenopathy, Organ function impairment due to disease involvement, Constitutional symptoms, Maximum diameter of disease > 7cm, >3 nodal sites of involvement, Risk of local compressive symptoms, Splenomegaly, Clinically significant pleural or peritoneal effusion, Leukemic phase, Rapid generalized disease progression, Renal infiltration, Bone lesions, Patients cannot be in need of urgent cytoreductive chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, Age ≥18 years.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Glofitamab (Monoclonal Antibodies)
• Obinutuzumab (Monoclonal Antibodies)

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.

Participant Groups

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.

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

Findings from Research

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]

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 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, 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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

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. [2019]

5. United States 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. [2021]

6. 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]

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

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study. [2023]

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

Glofitamab: First Approval. [2023]

9. 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]

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

Obinutuzumab for the treatment of indolent lymphoma. [2018]

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

Obinutuzumab: first global approval. [2021]