What is the mechanism of action of this treatment?

Common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies and targeted therapies. Monoclonal antibodies like obinutuzumab target specific antigens on lymphoma cells, leading to their destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Bispecific antibodies like glofitamab bind to both CD20 on B-cells and CD3 on T-cells, facilitating T-cell mediated killing of B-cells. These targeted approaches are important for NHL patients as they aim to eliminate cancer cells more precisely, potentially improving outcomes and reducing side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, such as monoclonal antibodies (e.g., obinutuzumab) and targeted therapies (e.g., glofitamab), often have side effects including infusion-related reactions (fever, chills, and hypotension), hematologic toxicities (neutropenia, anemia, and thrombocytopenia), and increased risk of infections. Other potential side effects include gastrointestinal symptoms (nausea, diarrhea), fatigue, and, less commonly, severe conditions like cytokine release syndrome and tumor lysis syndrome. Patients should discuss these risks with their healthcare provider to manage and mitigate side effects effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Hodgkin's Lymphoma, particularly those targeting CD20. Rituximab was one of the first anti-CD20 monoclonal antibodies approved, followed by obinutuzumab, which is a glycoengineered type II anti-CD20 antibody. More recently, glofitamab, a bispecific antibody targeting CD20 and CD3, has shown promise in clinical trials. These treatments work by targeting the CD20 antigen on B-cells, leading to cell lysis and apoptosis. Other approved treatments include CAR-T cell therapies like axicabtagene ciloleucel and tisagenlecleucel, which modify a patient's T-cells to target CD19 on B-cells.

What other types of research exist?

Promising alternatives to RO7227166 for Non-Hodgkin's Lymphoma patients include: 1) Venetoclax plus obinutuzumab, which has shown improved progression-free survival and acceptable tolerability in CLL/SLL patients. 2) ABT-526 combined with cytotoxic chemotherapy, which has demonstrated sustained activity in preclinical trials. 3) Hematopoietic cell transplantation (HCT) with reduced intensity or nonmyeloablative regimens, which has shown potential benefits in advanced CLL/SLL patients. These options should be discussed with a healthcare provider to determine the best course of action based on individual patient factors.

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Monoclonal Antibodies

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

Phase 1 & 2

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adverse events from prior anti-cancer therapy must have resolved to Grade </= 1

Must have at least one measureable target lesion (>/= 1.5 cm) in its largest dimension by computed tomography scan

Must not have

History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease

Significant cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up after end of study approximately every 3 months until death, loss to follow-up or study termination

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

Potential side effects may include reactions related to infusion such as fever or chills; immune system effects that could cause inflammation in various organs; increased risk of infection; fatigue; allergic reactions; and possible impact on blood counts leading to anemia or bleeding issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have a tumor larger than 1.5 cm detectable by CT scan.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have a serious heart condition.

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I have or had lymphoma or disease in my brain or spinal cord.

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I haven't had a live vaccine in the last 4 weeks and don't plan to during the study.

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I have had a solid organ transplant.

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My blood tests show high lymphocyte counts or abnormal cells, indicating lymphoma.

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I had a stem cell transplant using my own cells less than 100 days before starting obinutuzumab.

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I have had severe allergic reactions to antibody treatments and have a confirmed brain infection.

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I haven't had immunotherapy or similar treatments within the last 4 weeks or five half-lives of the drug before starting obinutuzumab.

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I have had a stem cell transplant and CAR-T cell therapy before.

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I do not have any active infections or recent major infections requiring hospitalization or IV antibiotics.

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I have not had another type of invasive cancer in the last 2 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ after end of study approximately every 3 months until death, loss to follow-up or study termination

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~after end of study approximately every 3 months until death, loss to follow-up or study termination

This trial's timeline: 3 weeks for screening, Varies for treatment, and after end of study approximately every 3 months until death, loss to follow-up or study termination for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Proportion of Participants with Adverse Event (AE)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Part IIIExperimental Treatment4 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 IIExperimental Treatment4 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 IExperimental Treatment3 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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Glofitamab

2021

Completed Phase 1

~60

Tocilizumab

2012

Completed Phase 4

~1840

Obinutuzumab

2014

Completed Phase 3

~3470

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies and targeted therapies. Monoclonal antibodies like obinutuzumab target specific antigens on lymphoma cells, leading to their destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Bispecific antibodies like glofitamab bind to both CD20 on B-cells and CD3 on T-cells, facilitating T-cell mediated killing of B-cells. These targeted approaches are important for NHL patients as they aim to eliminate cancer cells more precisely, potentially improving outcomes and reducing side effects compared to traditional chemotherapy.

[Staging and Treatment Response Evaluation in Malignant Lymphomas - Czech Lymphoma Study Group Recommendations According to Criteria Revised in 2014 (Lugano Classification)].