Mosunetuzumab for Chronic Lymphocytic Leukemia

Recruiting at33 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Hoffmann-La Roche

Must be taking: BTKi

Must not be taking: Immunosuppressives, Chemotherapy, Monoclonal antibodies, others

Disqualifiers: Pregnancy, Infections, HIV, others

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial allows participants who are currently taking a Bruton tyrosine kinase inhibitor (BTKi) to continue their medication during the screening period and for the first two cycles of mosunetuzumab. For other medications, the protocol does not specify, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Mosunetuzumab for treating chronic lymphocytic leukemia?

Mosunetuzumab has shown effectiveness in treating relapsed or refractory B-cell lymphomas, with high response rates in clinical trials for follicular lymphoma, suggesting potential benefits for similar conditions like chronic lymphocytic leukemia. ^{1 2 3 4 5}

Is Mosunetuzumab safe for humans?

Mosunetuzumab has been studied in patients with relapsed or refractory B-cell lymphomas, and it was generally well tolerated in these studies. While specific safety data for chronic lymphocytic leukemia is not available, the existing research suggests it is safe for human use in similar conditions. ^{3 4 5 6 7}

How is the drug Mosunetuzumab unique for treating chronic lymphocytic leukemia?

Mosunetuzumab is unique because it is a bispecific antibody that targets both CD20 and CD3, redirecting T cells to attack and eliminate cancerous B cells. This mechanism is different from traditional treatments, offering a novel approach to engaging the immune system in fighting the disease. ^{3 4 5 7 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Inclusion Criteria

I've been on a BTK inhibitor for 12+ months, my disease progressed on it, and I need more treatment.

My liver works well, unless its issues are caused by my CLL.

Life expectancy > 6 months

Exclusion Criteria

Participants specific to Arm C have received venetoclax therapy within 12 months prior to first study treatment administration, known infection with HIV or human T-cell leukemia virus 1 (HTLV1), uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia, received strong and moderate CYP3A inhibitors or inducers within 7 days prior to the initiation of study treatment, consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration, inability to swallow a large number of tablets, malabsorption syndrome or other condition that precludes enteral route of administration, known allergy to both xanthine oxidase inhibitors and rasburicase

I have not received a live vaccine within the last 4 weeks and won't need one during or within 5 months after the study.

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab monotherapy or a combination regimen with venetoclax or BTKi overlap therapy

12 weeks

Weekly visits for the first month, then bi-weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Mosunetuzumab (Monoclonal Antibodies)
• Tocilizumab (Immunosuppressive Agent)

Trial Overview 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.

Participant Groups

Group I: Arm C (non-US participants only) Experimental Treatment 3 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 B Experimental Treatment 2 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 A Experimental Treatment 2 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

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

Findings from Research

Alemtuzumab has shown significant efficacy in treating fludarabine-refractory chronic lymphocytic leukemia, achieving remissions with undetectable residual disease in patients, including those with poor prognostic factors.

Current research is exploring new applications for alemtuzumab, such as combining it with other treatments, using it for maintenance therapy, and purging bone marrow before transplantation, with several clinical trials underway to assess these strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. Rai, KR.[2017]

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., et al.[2023]

In a first-in-human trial involving 230 patients with relapsed or refractory B-cell non-Hodgkin lymphomas, mosunetuzumab demonstrated a manageable safety profile with common side effects like neutropenia and cytokine release syndrome, mostly low-grade and occurring primarily in the first treatment cycle.

The treatment showed promising efficacy, with overall response rates of 34.9% for aggressive and 66.2% for indolent B-NHL, and complete response rates of 19.4% and 48.5%, respectively, indicating that mosunetuzumab can induce durable responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. Budde, LE., Assouline, S., Sehn, LH., et al.[2023]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

Alemtuzumab has proven effective in treating chronic lymphocytic leukemia, both as a standalone treatment and in combination with other therapies like fludarabine or rituximab, showing improved response rates and survival compared to traditional chemotherapy.

Despite its efficacy, there are safety concerns due to known toxicities associated with alemtuzumab, particularly when used in combination therapies, which require careful management to avoid adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab: what is the secret to safe therapy? Elter, T., Hallek, M., Montillo, M.[2017]

In a Phase I study involving 23 Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, mosunetuzumab was found to be well tolerated, with no deaths reported and manageable side effects, primarily neutropenia and cytokine release syndrome.

The treatment showed promising antitumor activity, with 2 patients achieving complete responses and 11 achieving partial responses, indicating its potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Munakata, W., Izutsu, K., Mishima, Y., et al.[2023]

In a phase 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.

The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde, LE., Sehn, LH., Matasar, M., et al.[2022]

Mosunetuzumab, a T-cell-dependent bispecific antibody, is the first approved treatment for relapsed and refractory follicular lymphoma (FL), showing high efficacy and manageable side effects.

The review highlights the evolving treatment landscape for FL, emphasizing the potential of T-cell-redirecting therapies to improve outcomes for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma. Matarasso, S., Assouline, S.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Alemtuzumab: what is the secret to safe therapy? [2017]

6. England pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma. [2023]