Mosunetuzumab for Chronic Lymphocytic Leukemia

Recruiting at 44 trial locations

Overseen By Reference Study ID Number: BO43243 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

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 All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

137 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment called mosunetuzumab for people with chronic lymphocytic leukemia (CLL) that recurs or resists other treatments. The researchers aim to assess how well this treatment works alone and in combination with other drugs for those needing more options after unsuccessful therapies. Individuals with CLL who have tried two different treatments without success, particularly those currently on a Bruton tyrosine kinase inhibitor (a type of cancer drug) and needing another option, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mosunetuzumab, when used alone, is generally safe. Studies have found it rarely causes severe side effects, including a low risk of cytokine release syndrome (CRS), an overreaction of the immune system.

When combined with venetoclax, mosunetuzumab maintains a similar safety profile, with serious side effects remaining uncommon. Patients who continue their Bruton tyrosine kinase inhibitor (BTKi) treatment while starting mosunetuzumab can expect safety similar to using mosunetuzumab alone.

Overall, evidence suggests that mosunetuzumab, whether used alone or with other treatments, is generally well-tolerated in patients who have tried other therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Mosunetuzumab is unique because it works differently from standard treatments for chronic lymphocytic leukemia (CLL), such as BTK inhibitors and venetoclax. This investigational drug is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells, aiming to engage the body's immune cells to directly attack cancer cells. Unlike traditional therapies that may require multiple drugs or longer periods to show effectiveness, mosunetuzumab is administered subcutaneously, which can be more convenient and potentially improve patient compliance. Researchers are excited about its potential to offer a new, effective option for patients who have not responded to or have progressed on existing therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research shows that mosunetuzumab may help treat chronic lymphocytic leukemia (CLL) that has returned or hasn't responded to treatment. Earlier studies have observed long-lasting improvements and better survival rates in patients with conditions like CLL. In this trial, participants in Arm A will receive mosunetuzumab as a monotherapy. Arm B participants will receive mosunetuzumab with a Bruton tyrosine kinase inhibitor (BTKi) for the first two cycles, which might offer added benefits and enhance treatment effectiveness against leukemia. Meanwhile, Arm C, open only to non-US participants, will test mosunetuzumab with venetoclax, potentially boosting the immune system's ability to attack cancer cells. Overall, these treatments offer hope for patients who haven't had success with other therapies. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Tocilizumab

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.

How Is the Trial Designed?

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

Mosunetuzumab is already approved in European Union, United States for the following indications:

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05091424

NCT05091424 | A Study Evaluating the Safety, Efficacy, ... This study will assess the safety, tolerability, pharmaokinetics, and preliminary efficacy of mosunetuzumab (Lunsumio) monotherapy in participants with ...

2. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/leukemia/a-study-evaluating-the-safety--efficacy--and-pharmacoki-80734.html

Clinical Trial – Chronic Lymphocytic Leukemia – Efficacy,... Access the clinical trial testing the efficacy, safety and pharmacokinetics of mosunetuzumab in patients with relapsed or refractory chronic lymphocytic ...

3. ashpublications.org ashpublications.org/blood/article/145/7/708/525779/Long-term-3-year-follow-up-of-mosunetuzumab-in

Long-term 3-year follow-up of mosunetuzumab in relapsed or ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

4. lunsumio.com lunsumio.com/results/clinical-trial-results.html

Clinical trial results This study was a phase 2 clinical trial, meaning it studied an investigational treatment to test how well it worked and monitored for potential side effects ...

5. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4161706/paula.marlton.an.ongoing.phase.1b.trial.evaluating.mosunetuzumab.monotherapy.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3Dmosunetuzumab

AN ONGOING PHASE 1B TRIAL EVALUATING ... Mosunetuzumab monotherapy may have promise in R/R CLL and could exert synergistic activity when combined with the complementary mechanisms of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38195322/

Mosunetuzumab Safety Profile in Patients With Relapsed ... Conclusion: Mosunetuzumab monotherapy as treatment for R/R B-cell NHL, including FL, was associated with low rates of severe AEs (including CRS) and is suitable ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7014

Interim results from the phase II MorningSun study. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We ...