What is the mechanism of action of this treatment?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include bispecific antibodies like Mosunetuzumab, which target CD20 on B-cells and CD3 on T-cells to direct the immune system to attack cancer cells. BTK inhibitors (e.g., ibrutinib) block Bruton's tyrosine kinase, disrupting B-cell receptor signaling and leading to cancer cell death. BCL2 inhibitors (e.g., venetoclax) promote apoptosis by inhibiting the BCL2 protein that prevents cell death. These mechanisms are crucial for CLL patients as they offer targeted approaches to eliminate cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include bispecific antibodies like mosunetuzumab, BTK inhibitors such as ibrutinib, and BCL2 inhibitors like venetoclax. Mosunetuzumab can cause infusion-related reactions, cytokine release syndrome, and infections. Ibrutinib is associated with hematologic adverse effects, atrial fibrillation, hypertension, and infections. Venetoclax can lead to tumor lysis syndrome, neutropenia, and gastrointestinal issues. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Lymphocytic Leukemia (CLL), including monoclonal antibodies and targeted therapies. Rituximab, ofatumumab, and obinutuzumab are anti-CD20 monoclonal antibodies that have been used in CLL treatment. Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for CLL. Venetoclax, a BCL-2 inhibitor, is also approved for CLL, often in combination with obinutuzumab. While mosunetuzumab, a bispecific antibody targeting CD20 and CD3, is still under investigation, it represents a novel approach similar to these existing therapies.

What other types of research exist?

Promising alternatives to Mosunetuzumab for CLL patients include Bruton tyrosine kinase (BTK) inhibitors such as acalabrutinib and zanubrutinib, which are noted for their efficacy and tolerability. Venetoclax, a BCL2 inhibitor, is another effective option, especially when combined with obinutuzumab. These therapies offer targeted treatment approaches and have shown positive outcomes in clinical trials.

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Monoclonal Antibodies

Mosunetuzumab for Chronic Lymphocytic Leukemia

Phase 1

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

Diagnosis of CLL requiring treatment according to the International Workshop on CLL (iwCLL) criteria (Hallek et al 2018)

Eastern Cooperative Oncology Group (ECOG) performance score (PS) of ≤ 2

Must not have

History of prior malignancy except for conditions defined by the protocol

Contraindication to tocilizumab

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called mosunetuzumab, both alone and with another drug called venetoclax, in patients with a type of blood cancer that has come back or not responded to treatment. Mosunetuzumab helps the immune system attack cancer cells, while venetoclax helps kill the cancer cells. Venetoclax has been used with other drugs to help treat different types of blood cancers.

Who is the study for?

This trial is for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) who need treatment. They should have adequate bone marrow function, an ECOG score of ≤2, agree to use effective contraception, and have a life expectancy over 6 months. Exclusions include severe allergies to monoclonal antibodies, recent infections requiring IV antibiotics or hospitalization, pregnancy, prior specific cancer treatments within certain time frames.

What is being tested?

The study tests mosunetuzumab alone and in combination with venetoclax in CLL patients. It evaluates safety and initial effectiveness while allowing some participants to continue their current BTK inhibitor therapy during the first part of the trial. The pharmacokinetics—or how the body processes these drugs—is also being studied.

What are the potential side effects?

Potential side effects may include allergic reactions related to antibody treatment such as infusion reactions, liver issues due to tocilizumab contraindications (if applicable), and other common chemotherapy-related side effects like fatigue, nausea, blood disorders that could increase infection risk.

Eligibility Criteria

Inclusion Criteria

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

Select...

My CLL condition requires treatment.

Select...

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

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

Select...

I have had cancer before, but it meets the study's exceptions.

Select...

I cannot take tocilizumab due to health reasons.

Select...

I have not received treatments like mosunetuzumab or had an allogenic stem cell transplant before joining the study.

Select...

My CLL has transformed into an aggressive form of non-Hodgkin's lymphoma.

Select...

I haven't had any serious infections or been hospitalized for infections in the last month.

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%

Diarrhoea

35%

Anaemia

35%

Hypomagnesaemia

35%

Pyrexia

35%

Neuropathy peripheral

24%

Constipation

24%

Platelet count decreased

24%

Neutropenia

24%

Hypophosphataemia

24%

Nausea

24%

Liver function test abnormal

24%

Fatigue

24%

Thrombocytopenia

18%

Lethargy

18%

Hypokalaemia

18%

Arthralgia

18%

Weight decreased

18%

Neutrophil count decreased

18%

Oral candidiasis

18%

Sepsis

18%

Headache

18%

Peripheral sensory neuropathy

12%

Paraesthesia

12%

Vomiting

12%

Superficial vein thrombosis

12%

Rectal haemorrhage

12%

Flushing

12%

Cough

12%

Infusion related reaction

12%

Blood alkaline phosphatase increased

12%

Abdominal pain

12%

Pain in extremity

12%

Gastrooesophageal reflux disease

12%

Alanine aminotransferase increased

12%

Colitis

12%

Abdominal discomfort

12%

Dizziness

Adenocarcinoma

Hypocalcaemia

Chest pain

Dyspnoea exertional

Vasospasm

Gamma-glutamyltransferase increased

Orthostatic hypotension

Cellulitis

Wound infection

Hypogammaglobulinaemia

Abdominal distension

External ear cellulitis

Tumour lysis syndrome

Upper respiratory tract infection

Back pain

Urinary tract infection

Transient ischaemic attack

Hypertension

Blood creatinine increased

Abdominal tenderness

Seasonal allergy

Injury

Hypoalbuminaemia

Epistaxis

Throat irritation

Performance status decreased

Cytomegalovirus infection reactivation

Decreased appetite

Hyperlipidaemia

Hyperglycaemia

Oropharyngeal pain

Intention tremor

Rash

Thrombosis

Rash maculo-papular

Squamous cell carcinoma

Photosensitivity reaction

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: Arm C (non-US participants only)Experimental Treatment3 Interventions

Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax (this arm is open only to participants outside of the US)

Group II: Arm BExperimental Treatment2 Interventions

Participants with R/R CLL who have failed two prior lines of therapy, who are currently progressing on BTKi therapy, and who require salvage therapy as assessed by their treating physician will receive mosunetuzumab SC with BTKi overlap therapy for the first two cycles of mosunetuzumab SC

Group III: Arm AExperimental Treatment2 Interventions

Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2240

Mosunetuzumab

2019

Completed Phase 2

~140

Tocilizumab

2012

Completed Phase 4

~1840

0 / 7Eligibility 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 Chronic Lymphocytic Leukemia (CLL) include bispecific antibodies like Mosunetuzumab, which target CD20 on B-cells and CD3 on T-cells to direct the immune system to attack cancer cells. BTK inhibitors (e.g., ibrutinib) block Bruton's tyrosine kinase, disrupting B-cell receptor signaling and leading to cancer cell death. BCL2 inhibitors (e.g., venetoclax) promote apoptosis by inhibiting the BCL2 protein that prevents cell death. These mechanisms are crucial for CLL patients as they offer targeted approaches to eliminate cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

The latest developments with anti-CD20 monoclonal antibodies in chronic lymphocytic leukemia.