Mosunetuzumab Clinical Trials

What Is Mosunetuzumab?

Mosunetuzumab is an FDA-approved medication for follicular lymphoma. It is a type of bispecific antibody, which means it is designed to target two different proteins at once. Mosunetuzumab specifically targets CD20, a protein found on the surface of B-cells, including cancerous lymphoma cells, and CD3, a protein found on T-cells, which are immune cells. By binding to both CD20 and CD3, mosunetuzumab helps bring T-cells closer to lymphoma cells, enabling the immune system to recognize and destroy the cancer cells.

Mosunetuzumab is currently being investigated in 54 clinical trials with a total enrollment of 6,887 participants. These trials began as early as 2015 and are projected to continue until at least 2026. It is being studied both as a standalone treatment and in combination with other therapies for various blood cancers and autoimmune conditions.

Uses and Conditions Under Study

Mosunetuzumab is primarily being studied for the treatment of various lymphomas, which are cancers that begin in infection-fighting cells of the immune system called lymphocytes. Follicular lymphoma is a specific type of non-Hodgkin lymphoma that grows slowly. Mosunetuzumab is being investigated in 9 trials for follicular lymphoma, and an additional 9 trials for specific grades of follicular lymphoma (Grade 1, Grade 2, and Grade 3a). The drug's mechanism of targeting CD20 on B-cells is particularly relevant for these conditions, as follicular lymphoma originates from B-lymphocytes.

Beyond follicular lymphoma, mosunetuzumab is also under investigation for other types of lymphoma. This includes 4 trials for non-Hodgkin lymphoma, 3 trials for general lymphoma, 3 trials for B-cell lymphoma, 3 trials for marginal zone lymphoma, and 2 trials for diffuse large B-cell lymphoma. These conditions also involve abnormal B-cells, suggesting that mosunetuzumab's targeted action could be beneficial across a range of B-cell malignancies.

In addition to its use in oncology, mosunetuzumab is being studied for its potential in autoimmune diseases, specifically in 2 trials for systemic lupus erythematosus. Systemic lupus erythematosus is a chronic autoimmune disease where the immune system mistakenly attacks healthy tissues. Given that B-cells play a significant role in the immune response and can contribute to autoimmune activity, targeting these cells with mosunetuzumab may help modulate the disease.

Dosing

Mosunetuzumab has been studied in clinical trials for administration through both intravenous (IV) infusion and subcutaneous (SC) injection. The specific dosage and schedule can vary depending on the condition being treated and whether it is given as a single agent or in combination with other drugs.

One studied intravenous regimen involves a step-up dosing approach in the first cycle: 1 mg on Day 1, 2 mg on Day 8, and 30 mg on Day 15. From Cycle 2 onwards, 30 mg is typically given on Day 1. Each treatment cycle for this regimen is 28 days, and treatment may continue for up to 8 to 12 cycles based on efficacy evaluations. Another dose of 200 mg daily has also been explored in some studies.

Mosunetuzumab is frequently investigated in combination with other therapies. These combinations include drugs such as tazemetostat, pirtobrutinib, tislelizumab, zanubrutinib, lenalidomide, polatuzumab vedotin, and various chemotherapy regimens like CHOP or EPOCH. The specific dosing strategy, including whether it is given inpatient or outpatient, is tailored to the particular study design and the patient's condition. All studies with mosunetuzumab have focused on adult patients.

Side Effects

In a study (NCT04313608) of patients with relapsed or refractory diffuse large B-cell lymphoma and high-grade large B-cell lymphoma, the most common serious side effects for Mosunetuzumab in combination with gemcitabine and oxaliplatin (Mosun-GemOx) were:

• Serious adverse events (SAEs) occurred in 66.7% of patients taking Mosun-GemOx, compared to 70.6% of patients taking glofitamab with gemcitabine and oxaliplatin (Glofit-GemOx).
• Cytokine Release Syndrome (CRS) was reported in 16.7% of patients receiving Mosun-GemOx. All cases were Grade 1 (mild). In comparison, 47.1% of patients on Glofit-GemOx experienced CRS, with cases up to Grade 3 (severe).

Other side effects and treatment modifications observed in this study included:

• Dose reductions due to adverse events occurred in 50.0% of Mosun-GemOx patients, compared to 29.4% of Glofit-GemOx patients.
• Dose interruptions due to adverse events occurred in 16.7% of Mosun-GemOx patients, compared to 5.9% of Glofit-GemOx patients.
• Treatment discontinuations due to adverse events occurred in 16.7% of Mosun-GemOx patients, compared to 5.9% of Glofit-GemOx patients.
• No deaths due to adverse events were reported in the Mosun-GemOx group, while 5.9% of patients in the Glofit-GemOx group experienced a death due to an adverse event.

In a separate Phase 1b study (NCT05315713) evaluating a subcutaneous formulation of Mosunetuzumab in combination with intravenous tiragolumab for B-cell non-Hodgkin lymphoma, 100% of participants experienced at least one adverse event.

Clinical Trial Results

Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

In an interim analysis of a study (NCT05171647) comparing Mosunetuzumab plus polatuzumab vedotin (Mosun-Pola) to rituximab plus gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma:

• The objective response rate (ORR), meaning the proportion of patients who experienced a partial or complete response, was 69.7% for patients treated with Mosun-Pola, compared to 44.1% for those treated with R-GemOx.
• The median progression-free survival (PFS), which is the time patients lived without their cancer getting worse, was 11.5 months for the Mosun-Pola group, significantly longer than the 3.8 months observed in the R-GemOx group.

Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

A study (NCT04313608) evaluated Mosunetuzumab in combination with gemcitabine and oxaliplatin (Mosun-GemOx) against glofitamab with gemcitabine and oxaliplatin (Glofit-GemOx) in patients with relapsed or refractory diffuse large B-cell lymphoma and high-grade large B-cell lymphoma:

• The objective response rate (ORR) was 50.0% for patients receiving Mosun-GemOx, compared to 35.3% for those on Glofit-GemOx.
• A complete response (CR) was achieved by 50.0% of patients in the Mosun-GemOx arm, versus 23.5% in the Glofit-GemOx arm.

B-Cell Non-Hodgkin Lymphoma (First-line Treatment)

A Phase Ib/II study (NCT03677141) investigated Mosunetuzumab in combination with chemotherapy regimens for B-cell non-Hodgkin lymphoma:

• When Mosunetuzumab was combined with CHP-polatuzumab vedotin (Mosun + CHP-Pola), the objective response rate (ORR) was 80.0%, compared to 77.3% for patients treated with rituximab plus CHP-polatuzumab vedotin (Rituximab + CHP-Pola).
• The complete response (CR) rate in the Mosun + CHP-Pola group was 72.5%, while it was 77.3% in the Rituximab + CHP-Pola group.
• For patients treated with Mosunetuzumab plus CHOP (Mosun + CHOP), the best overall response rate was 95.0%, and the 1-year progression-free survival was 77.47%.

Untreated Indolent B-Cell Non-Hodgkin Lymphoma

In a study (NCT05169658) of Mosunetuzumab in combination with polatuzumab vedotin and obinutuzumab for untreated indolent B-cell non-Hodgkin lymphoma, 42 participants achieved an overall response, and 38 participants achieved a complete response.

B-Cell Non-Hodgkin Lymphoma (Subcutaneous Formulation)

A Phase 1b study (NCT05315713) evaluating a subcutaneous formulation of Mosunetuzumab combined with intravenous tiragolumab in B-cell non-Hodgkin lymphoma showed an objective response rate of 62.5% and a complete response rate of 37.5%.

Currently Recruiting Trials

Mosunetuzumab is currently being investigated in numerous clinical trials for a variety of conditions, offering potential new treatment options. These studies aim to understand its safety and effectiveness, sometimes alone and often in combination with other therapies.

One ongoing Phase 2 study, NCT07598396, sponsored by Hoffmann-La Roche, is evaluating mosunetuzumab in participants with systemic lupus erythematosus, including those who also have active lupus nephritis. This trial is designed for 30 individuals.

For patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), a Phase 1/Phase 2 study, NCT07052695, is testing mosunetuzumab either alone or combined with a Bruton tyrosine kinase inhibitor (BTKi). This study targets an enrollment of 40 participants.

Several large Phase 3 trials are underway for follicular lymphoma. The National Cancer Institute is sponsoring NCT06337318, which compares mosunetuzumab to rituximab in patients with low tumor burden follicular lymphoma, aiming for 600 participants. Another Phase 3 study, NCT06284122, from The Lymphoma Academic Research Organisation, is comparing mosunetuzumab plus lenalidomide against anti-CD20 antibody plus chemotherapy in previously untreated follicular lymphoma patients, with a target enrollment of 790.

In the realm of diffuse large B-cell lymphoma (DLBCL), a Phase 2 study, NCT06828991, is assessing mosunetuzumab as a consolidation therapy for older patients who have detectable circulating tumor DNA (ctDNA) after initial treatment. This study plans to include 40 participants.

For newly diagnosed extranodal marginal zone lymphoma, a Phase 2 trial, NCT06569680, is investigating mosunetuzumab as a first-line treatment for 35 patients. Additionally, a Phase 3 trial, NCT06006117, is comparing mosunetuzumab-lenalidomide to investigator's choice regimens for 260 patients with relapsed or refractory marginal zone lymphoma.

Where to Participate

Clinical trials for mosunetuzumab are widely available across the United States, with study sites spanning 47 states. In total, there are 391 sites across 258 cities actively recruiting participants. This broad geographic reach helps make participation accessible to many individuals.

Some of the cities with the highest number of recruiting sites include:

• New York, New York (12 sites)
• Portland, Oregon (9 sites)
• Miami, Florida (8 sites)
• Atlanta, Georgia (8 sites)
• Houston, Texas (7 sites)
• Charlotte, North Carolina (7 sites)

Most of these studies are seeking adult participants, generally between the ages of 18 to 80 years. All genders are eligible to participate, but these trials are not open to healthy volunteers or children, as they focus on specific patient populations with the conditions being studied.

Development Timeline

The journey of mosunetuzumab in clinical development began on 2015-07-16, marking the start of its first clinical trial. Since then, the development program has grown significantly, with a total of 54 trials initiated and a collective enrollment target of 6,887 participants. The latest trial is projected to conclude in 2026.

Initially, mosunetuzumab was explored for conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and expanded into a broad range of B-cell malignancies and autoimmune diseases. Hoffmann-La Roche has been a primary driver of this research, sponsoring 12 studies, with other institutions like M.D. Anderson Cancer Center, the University of Washington, and the National Cancer Institute also playing key roles.

The development has progressed through various phases, with the majority of studies being Phase 2 (28 trials) and Phase 1/Phase 2 (11 trials). There are also 9 Phase 1 trials and 5 Phase 3 trials, indicating advanced stages of research for some indications. The pipeline has expanded to include a wide array of conditions such as follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, and systemic lupus erythematosus. This expansion reflects a growing understanding of mosunetuzumab's potential across different diseases where B-cell targeting may be beneficial.