RO7227166 + Obinutuzumab + Glofitamab for Non-Hodgkin's Lymphoma

Recruiting at 42 trial locations

Overseen By Reference Study ID Number: BP41072 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Immunotherapeutics

Disqualifiers: Infections, Transplants, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

498 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like systemic immunotherapeutic agents or chemotherapy within 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination RO7227166, Obinutuzumab, and Glofitamab for Non-Hodgkin's Lymphoma?

Research shows that Obinutuzumab, a part of this drug combination, has been effective in treating follicular lymphoma, especially in patients who did not respond to or relapsed after other treatments. It has been shown to improve progression-free survival and overall survival when combined with other drugs in clinical studies. ^{1 2 3 4 5}

What safety data exists for Obinutuzumab in treating Non-Hodgkin's Lymphoma?

Obinutuzumab, used in treating Non-Hodgkin's Lymphoma, generally has manageable side effects, with mild to moderate infusion-related reactions (like fever or chills during the drug infusion) being common. More serious side effects include neutropenia (a drop in white blood cells), but these are less frequent. ^{2 3 5 6 7}

What makes the drug combination of RO7227166, Obinutuzumab, and Glofitamab unique for treating Non-Hodgkin's Lymphoma?

This drug combination is unique because it includes Obinutuzumab, a novel anti-CD20 antibody that has shown improved efficacy over rituximab, especially in patients who are resistant to rituximab. Obinutuzumab is designed to induce strong direct cell death and enhance the immune system's ability to kill cancer cells, making it a promising option for difficult-to-treat cases of Non-Hodgkin's Lymphoma. ^{2 3 4 5 8}

What is the purpose of this trial?

This trial is testing a new drug called RO7227166, given through an IV, along with two other drugs, obinutuzumab and glofitamab. Obinutuzumab is a monoclonal antibody recently approved for treating follicular lymphoma that has relapsed or was refractory to a rituximab-containing regimen. It targets patients whose Non-Hodgkin's Lymphoma has come back or didn't respond to previous treatments. The goal is to see if this combination can help the immune system fight the cancer more effectively.

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 two prior treatments and have no other survival-prolonging options. They must not be pregnant or breastfeeding, agree to contraception requirements, have a life expectancy of over 12 weeks, and good organ function. Exclusions include active infections, recent major surgery or immunotherapy, certain cardiovascular diseases, and CNS lymphoma.

Inclusion Criteria

Life expectancy of >/= 12 weeks

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

Side effects from my previous cancer treatments are mild or gone.

Exclusion Criteria

I haven't had cancer treatment within the last 4 weeks or before the drug's half-life period, whichever is shorter, before starting obinutuzumab.

I've had side effects from previous immune treatments or have an autoimmune disease.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

A fixed dose of obinutuzumab is administered up to seven days prior to the first administration of englumafusp alfa and glofitamab

1 week

Dose-Escalation

Participants receive englumafusp alfa in combination with obinutuzumab or glofitamab in a three-weekly schedule

Part I: Up to 24 months; Part II: Up to 18 months

Dose-Expansion

Participants receive englumafusp alfa in combination with glofitamab in a three-weekly schedule

Part III: Up to 9 months or up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Glofitamab
• Obinutuzumab
• RO7227166

Trial Overview The study tests RO7227166 combined with obinutuzumab and glofitamab in people with specific lymphomas. It starts with a pre-treatment dose of obinutuzumab followed by the main drugs in escalating doses to find safe levels (Phase I/II) before expanding to more patients (Phase III).

Participant Groups

Group I: Part III Experimental Treatment 4 Interventions

Dose-Expansion Stage: Participants with r/r diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from FL (transformed FL) will receive englumafusp alfa administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).

Group II: Part II Experimental Treatment 4 Interventions

Combination Dose-Escalation: Mixed r/r participants and participants with mixed r/r mantle cell lymphoma (MCL) and Richters transformation will receive a fixed dose of obinutuzumab seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by IV infusion in combination with glofitamab in a three-weekly schedule (Q3W).

Group III: Part I Experimental Treatment 3 Interventions

Combination Dose-Escalation: Mixed r/r NHL participants will receive a fixed dose of obinutuzumab up to seven days prior to first administration of englumafusp alfa. Englumafusp alfa will be administered by intravenous (IV) infusion in combination with obinutuzumab in a three-weekly schedule (Q3W).

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

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]

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 phase 2 study involving 89 patients with relapsed or refractory follicular lymphoma, 79% achieved an overall response after treatment with lenalidomide and obinutuzumab, demonstrating significant efficacy in this patient population.

The treatment had a manageable safety profile, with common adverse events including neutropenia and asthenia, and serious adverse events reported in 34% of patients, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Morschhauser, F., Le Gouill, S., Feugier, P., et al.[2019]

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 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 is a newly approved monoclonal antibody for treating chronic lymphocytic leukemia (CLL) in combination with chlorambucil, showing improved efficacy compared to the older drug rituximab.

In a phase III study, patients treated with obinutuzumab plus chlorambucil experienced deeper and longer remissions, with better progression-free survival and higher rates of complete and molecular responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab for chronic lymphocytic leukemia: promise of the first treatment approved with breakthrough therapy designation. Kakkar, AK., Balakrishnan, S.[2015]

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]

References

1. 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]

2. France pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. [2019]

5. 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]

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. England pubmed.ncbi.nlm.nih.gov

Obinutuzumab for chronic lymphocytic leukemia: promise of the first treatment approved with breakthrough therapy designation. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Obinutuzumab for the treatment of indolent lymphoma. [2018]