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

Recruiting at 57 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with certain types of Non-Hodgkin's Lymphoma, a cancer affecting the lymphatic system, that have returned or not responded to previous treatments. The study aims to determine if the combination of englumafusp alfa (also known as RO7227166), obinutuzumab, and glofitamab is safe and effective. Participants will receive these drugs through an IV infusion, with different groups testing various combinations. This trial may suit those who have tried at least one treatment for their lymphoma and have no other expected options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Research has shown that the treatments in this trial have varying safety levels based on past studies. The new drug, RO7227166 (also called englumafusp alfa), is still under investigation, so detailed safety information remains limited. As this is an early phase trial, researchers are determining the optimal dose and monitoring for side effects.

Glofitamab, another drug in this trial, has undergone more extensive study. While it can be effective, more than half of the patients experienced serious side effects, which are significant medical issues. However, these side effects were considered manageable in patients who had already received extensive treatment.

Obinutuzumab is a more established treatment. Previous studies have shown it to be safer compared to some similar treatments, and it is already approved for certain types of lymphoma, providing more confidence in its safety.

Overall, each drug has its own safety profile. Some have more data supporting their safety, while others are still being studied to better understand their effects. Participants should consider these factors and discuss them with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-Hodgkin's lymphoma because they offer new ways to tackle the disease. Unlike standard treatments like chemotherapy and rituximab, these investigational therapies involve a novel combination of drugs: Glofitamab, Obinutuzumab, and RO7227166. Glofitamab and RO7227166 work by engaging the immune system in a unique way, aiming to boost its ability to target and destroy cancer cells more effectively. Obinutuzumab is an engineered antibody that targets a specific protein on B-cells, potentially leading to more precise attacks on lymphoma cells. This innovative approach could lead to more effective treatments with fewer side effects compared to conventional options.

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

This trial will evaluate the combination of RO7227166, Obinutuzumab, and Glofitamab for Non-Hodgkin's Lymphoma. Studies have shown that Glofitamab effectively treats diffuse large B-cell lymphoma (DLBCL), with over half of the patients responding positively. It is approved in more than 30 countries for use when other treatments have not worked. Obinutuzumab has also improved tumor response and delayed disease progression in B-cell cancers like DLBCL and mantle cell lymphoma. Englumafusp alfa (RO7227166) is a new drug targeting CD19, a marker on B-cells, and early research suggests it may help treat relapsed or hard-to-treat Non-Hodgkin's Lymphoma (NHL). This trial will explore the potential of combining these treatments to enhance their individual effects, offering hope for those with challenging forms of NHL. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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, 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]

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]

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]

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]

Citations

1. 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.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... Glofit-Pola demonstrated high efficacy and durable responses, with manageable safety, in heavily pretreated patients with R/R LBCL, including ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7773/528089/Real-World-Data-of-Glofitamab-in-Relapsed

Real World Data of Glofitamab in Relapsed Refractory Large ... The presented data is reassuring that Glofitamab has an important role in the treatment of relapse refractory DLBCL, a real-world experience mainly of patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12208169/

New bispecific antibodies in diffuse large B-cell lymphoma Epcoritamab and glofitamab have both been approved in over 30 countries as monotherapy for DLBCL after two prior treatment lines; odronextamab has recent ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03533283

Study Details | NCT03533283 | An Open-Label Phase lB/II ... An Open-Label Phase lB/​II Study of Glofitamab and Atezolizumab or Polatuzumab Vedotin in Adult Patients With Relapsed/​Refractory B-Cell Non-Hodgkin's Lymphoma.

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/893/502948/Glofitamab-Monotherapy-in-Patients-with-Non

Glofitamab Monotherapy in Patients with Non-Hodgkin B-Cell ... We report the results of the primary analysis of a phase II multicenter study using glofitamab in pts with R/R non-Hodgkin B-cell lymphoma after CAR T-cell ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602510/

Glofitamab (Columvi) - NCBI Bookshelf Indication: For the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, trFL, or PMBCL, who have received 2 or more lines ...

8. firstwordpharma.com firstwordpharma.com/story/5991182

Health Canada Approves Roche's Columvi (glofitamab) as ... In 2023, Columvi was approved as a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma ( ...