What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, including T-Cell bispecific antibodies like Glofitamab, often lead to side effects such as cytokine release syndrome (CRS), which can cause fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. Other potential side effects include infections due to immunosuppression, infusion-related reactions, and hematologic toxicities like neutropenia, anemia, and thrombocytopenia. General chemotherapy side effects, such as gastrointestinal disturbances, fatigue, and hair loss, may also occur.

What prior FDA approvals exist?

The FDA has approved several therapies for the treatment of Non-Hodgkin's Lymphoma (NHL), particularly those targeting CD20. Rituximab, a monoclonal antibody targeting CD20, was one of the first and has been widely used. Other CD20-targeting monoclonal antibodies include obinutuzumab and ofatumumab. More recently, bispecific antibodies like mosunetuzumab, which also targets CD20 and CD3, have been explored in clinical trials. These therapies, often used in combination with other agents, have significantly advanced the treatment landscape for NHL.

What other types of research exist?

Promising novel alternatives to Glofitamab for Non-Hodgkin's Lymphoma patients include: 1) Mosunetuzumab, another T-cell engaging bispecific antibody targeting CD20 and CD3, which has shown efficacy in clinical trials. 2) Loncastuximab tesirine, an antibody-drug conjugate targeting CD19, which has been approved for relapsed or refractory large B-cell lymphoma. 3) CAR T-cell therapies such as Axicabtagene ciloleucel and Tisagenlecleucel, which target CD19 and have demonstrated significant efficacy in relapsed or refractory NHL.

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T-Cell Bispecific Antibody

Glofitamab + Obinutuzumab 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

No available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [ASCT])

Measurable disease defined as at least one bi-dimensionally measurable nodal lesion (> 1.5 cm) or at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm)

Must not have

Known active infection, reactivation of a latent infection, or major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing

Refactoriness to an obinutuzumab-containing regimen

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests glofitamab, a new drug given through an IV that helps immune cells attack cancer cells. It targets patients who need new treatment options because their cancer hasn't responded to existing treatments. The drug works by connecting immune cells to cancer cells, making it easier for the immune system to destroy the cancer. Glofitamab shows promise in treating certain types of blood cancers.

Who is the study for?

This trial is for adults with relapsed/refractory B-Cell Non-Hodgkin's Lymphoma who've had at least one prior treatment and lack other survival-prolonging options. Participants must have measurable disease, be in good physical condition (ECOG 0 or 1), and have proper liver, kidney, and blood function. Pregnant women are excluded, as well as those with certain infections or a history of severe reactions to similar drugs.

What is being tested?

The study tests Glofitamab alone or combined with Obinutuzumab in patients pre-treated with a fixed dose of Obinutuzumab. It's an early-phase trial to find the safest and most effective doses (Phase I/II). The trial includes escalating doses followed by expansion cohorts once optimal dosing is determined.

What are the potential side effects?

Potential side effects include allergic reactions to the drugs, possible organ inflammation due to immune response, fatigue, changes in blood counts that could affect immunity or clotting, infusion-related reactions during drug administration, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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I have no treatment options left that could extend my life.

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I have a tumor that can be measured with imaging tests.

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

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My blood cancer is likely to have CD20.

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My condition did not improve after at least one treatment.

Exclusion Criteria

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

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I have not had a serious infection or been on IV antibiotics in the last 4 weeks.

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My condition did not improve after treatment with obinutuzumab.

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I had a stem cell transplant using my own cells less than 100 days ago.

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I have had progressive multifocal leukoencephalopathy or CNS lymphoma.

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I've had side effects from previous immune therapy.

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My condition is either CLL, Burkitt lymphoma, or lymphoplasmacytic lymphoma.

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I have or might have had HLH.

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I have a significant history of heart disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2021 Phase 1 trial • 23 Patients • NCT04313608

41%

Cytokine release syndrome

35%

Anaemia

35%

Diarrhoea

35%

Hypomagnesaemia

35%

Pyrexia

35%

Neuropathy peripheral

24%

Neutropenia

24%

Platelet count decreased

24%

Nausea

24%

Liver function test abnormal

24%

Hypophosphataemia

24%

Constipation

24%

Fatigue

24%

Thrombocytopenia

18%

Oral candidiasis

18%

Lethargy

18%

Weight decreased

18%

Neutrophil count decreased

18%

Arthralgia

18%

Hypokalaemia

18%

Sepsis

18%

Headache

18%

Peripheral sensory neuropathy

12%

Paraesthesia

12%

Vomiting

12%

Superficial vein thrombosis

12%

Rectal haemorrhage

12%

Flushing

12%

Infusion related reaction

12%

Alanine aminotransferase increased

12%

Cough

12%

Blood alkaline phosphatase increased

12%

Abdominal pain

12%

Pain in extremity

12%

Gastrooesophageal reflux disease

12%

Colitis

12%

Abdominal discomfort

12%

Dizziness

Dyspnoea exertional

Photosensitivity reaction

Wound infection

Gamma-glutamyltransferase increased

Chest pain

Orthostatic hypotension

Cellulitis

Hypogammaglobulinaemia

Adenocarcinoma

External ear cellulitis

Tumour lysis syndrome

Vasospasm

Abdominal distension

Urinary tract infection

Transient ischaemic attack

Hypertension

Blood creatinine increased

Abdominal tenderness

Seasonal allergy

Injury

Hypoalbuminaemia

Performance status decreased

Hyperlipidaemia

Upper respiratory tract infection

Hyperglycaemia

Epistaxis

Squamous cell carcinoma

Oropharyngeal pain

Intention tremor

Hypocalcaemia

Decreased appetite

Throat irritation

Rash

Thrombosis

Rash maculo-papular

Cytomegalovirus infection reactivation

Back pain

Depression

Neutropenic sepsis

Vision blurred

Abdominal pain lower

Anal haemorrhage

Aspartate aminotransferase increased

Groin pain

Pain in jaw

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Glofit-GemOx

Arm B: Mosun-GemOx

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 III: Dose ExpansionExperimental Treatment3 Interventions

Part III will start once MTD/OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7 (pre-treatment), followed by glofitamab at a fixed dose regimen or step-up dose regimen on a Q2W or Q3W dosing schedule as determined in Part II. A total of 12 cycles will be administered. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with glofitamab at the dosing regimen determined in Part II.

Group II: Part II: Dose EscalationExperimental Treatment3 Interventions

In each treatment regimen, participants will receive obinituzumab (Gpt) 1000 milligrams (mg) IV infusion on Day -7 (pre-treatment); or 2000 mg either administered on Day -7, or split into two 1000 mg doses on Days -1 and -7. The first glofitamab IV infusion will be given on Day 1 of Cycle 1 and a total of 12 cycles will be administered. Monotherapy, glofitamab as a single agent: ascending doses of glofitamab administered on Day 1 of every 2 or 3 week cycle until either the MTD/OBD is defined. Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg obinutuzumab will be administered via IV infusion in combination with ascending doses of glofitamab on Day 1 of every 3 week cycle until either the MTD/OBD is defined. Step-up dosing: Q3W, participants will receive an initial low dose of glofitamab on C1D1, followed by a higher dose on C1D8; the total dose in C1 will not exceed the previously determined MTD. Higher doses may be explored from C2 or later cycles.

Group III: Part I: Dose EscalationExperimental Treatment3 Interventions

Participants (single participant cohorts) will receive obinutuzumab (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 (pre-treatment) followed by glofitamab IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of glofitamab will be administered on Day 1 of every 2 week cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. Glofitamab dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Glofitamab

2021

Completed Phase 1

~60

Obinutuzumab

2014

Completed Phase 3

~3470

Tocilizumab

2012

Completed Phase 4

~1840

0 / 13Eligibility 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

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapies. Monoclonal antibodies, such as rituximab and obinutuzumab, target specific antigens like CD20 on the surface of B-cells, leading to their destruction. Bispecific T-cell engagers, like Glofitamab, simultaneously bind to CD20 on B-cells and CD3 on T-cells, bringing T-cells into close proximity with B-cells to facilitate targeted killing. CAR T-cell therapies involve modifying a patient's T-cells to express receptors that specifically target and destroy cancer cells. These treatments are crucial for NHL patients as they offer targeted, effective options that can lead to better outcomes and potentially fewer side effects compared to traditional chemotherapy.