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 2023 Phase 1 & 2 trial • 117 Patients • NCT03677141

58%

Cytokine release syndrome

45%

Nausea

37%

Neutropenia

32%

Fatigue

32%

Diarrhoea

29%

Neutrophil count decreased

29%

Decreased appetite

26%

Alanine aminotransferase increased

24%

Anaemia

24%

Vomiting

24%

Infusion related reaction

18%

Alopecia

16%

Aspartate aminotransferase increased

16%

White blood cell count decreased

16%

Dizziness

16%

Dyspepsia

16%

Thrombocytopenia

16%

Abdominal pain

16%

Rash

16%

Constipation

13%

Back pain

13%

Febrile neutropenia

13%

Peripheral sensory neuropathy

13%

Oedema peripheral

11%

Hypophosphataemia

11%

Platelet count decreased

11%

Weight decreased

11%

Pruritus

11%

Dyspnoea

11%

Pyrexia

11%

Hypokalaemia

11%

Hypomagnesaemia

Infection

Hyponatraemia

Lymphopenia

Urinary tract infection

Stomatitis

Neuropathy peripheral

Tachycardia

Asthenia

Hyperglycaemia

Dehydration

Dysgeusia

Paraesthesia

Dysuria

Pollakiuria

Vision blurred

Hypertension

Hypotension

Gamma-glutamyltransferase increased

Headache

Hyperuricaemia

Arthralgia

Rhinorrhoea

Death

Herpes zoster

Leukocytosis

Vertigo

Rash maculo-papular

Liver function test increased

Hypoalbuminaemia

Gastrooesophageal reflux disease

Insomnia

Diverticulum intestinal haemorrhagic

Hypertransaminasaemia

Acute pulmonary oedema

Cytomegalovirus infection reactivation

Syncope

Atrial fibrillation

Atrial flutter

Blood alkaline phosphatase increased

Blood bilirubin increased

Blood lactate dehydrogenase increased

Vitamin D deficiency

Pain in extremity

Restlessness

Urinary incontinence

Acute kidney injury

Muscular weakness

Myalgia

Dry skin

Cardiac failure

Coma

Nail disorder

Hepatic encephalopathy

Hyperhidrosis

Angina unstable

Neutropenic colitis

Mucosal inflammation

Gastroenteritis norovirus

Klebsiella infection

Troponin I increased

Cerebrovascular accident

Pneumonitis

Pulmonary haemorrhage

Chest discomfort

Urticaria

Chills

Pain

Blood creatinine increased

International normalised ratio increased

Lymphocyte count decreased

Hypoaesthesia

Tremor

COVID-19

Hypocalcaemia

Respiratory failure

Taste disorder

Ulcer

Anastomotic ulcer

Fistula

100%

80%

60%

40%

20%

Study treatment Arm

Arm 1: Phase II Mosunetuzumab + CHP-Pola (Randomized)

Group A1: Phase Ib Mosunetuzumab + CHOP

Group A2: Phase Ib Mosunetuzumab + CHOP

Group B: Phase Ib Mosunetuzumab + CHP-Pola

Group C: Phase II Mosunetuzumab + CHOP

Arm 2: Phase II Rituximab + CHP-Pola (Randomized)

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.