Mosunetuzumab + Polatuzumab Vedotin for Diffuse Large B-Cell Lymphoma

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must be taking: Entecavir prophylaxis

Must not be taking: Immunosuppressants, Methotrexate

Disqualifiers: Neuropathy, Transplant history, CNS disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of drugs, including mosunetuzumab and polatuzumab vedotin, improves treatment outcomes for individuals newly diagnosed with diffuse large B-cell lymphoma, a type of blood cancer. Participants will receive these drugs alongside a standard chemotherapy regimen. The trial specifically seeks older adults, aged 70-74, who have been diagnosed with this cancer and have not yet received treatment. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressant therapy for an active autoimmune disease, you may not be eligible unless exceptions apply. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of mosunetuzumab and polatuzumab vedotin is generally safe for patients. Studies have found that most people do not experience serious side effects from this treatment. Earlier trials tested this combination on patients ineligible for transplants, and it proved safe and effective. While some side effects can occur, they are usually manageable. Researchers are also studying this treatment in older and more fragile patients with diffuse large B-cell lymphoma, further supporting its safety across different patient groups. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for diffuse large B-cell lymphoma?

Researchers are excited about Mosunetuzumab and Polatuzumab Vedotin for diffuse large B-cell lymphoma because these treatments offer a novel approach compared to the traditional chemotherapy regimens like R-CHOP. Mosunetuzumab is a bispecific antibody that uniquely targets and binds to both the cancer cells and T-cells, effectively bringing them together to destroy the tumor. Polatuzumab Vedotin, on the other hand, is an antibody-drug conjugate that delivers a potent chemotherapy directly to the cancer cells, minimizing damage to healthy cells. This combination has the potential to improve outcomes by directly targeting the lymphoma cells more efficiently than standard treatments.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

Research has shown that the combination of mosunetuzumab and polatuzumab vedotin, which participants in this trial will receive, holds promise for treating diffuse large B-cell lymphoma, particularly in patients who have relapsed or not responded to previous treatments. This combination outperforms other treatments, significantly improving response rates and reducing the risk of disease progression or death by 59%. Mosunetuzumab aids the immune system in identifying and destroying cancer cells, while polatuzumab vedotin delivers a toxin directly to these cells to kill them. This combination has proven effective and generally safe for patients. Overall, the evidence suggests that this treatment could greatly improve patient outcomes. ^{2 3 6 7 8}

Who Is on the Research Team?

Nirav Shah, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for elderly patients newly diagnosed with diffuse large B-cell lymphoma. Specific eligibility details are not provided, but typically participants must meet certain health criteria and have no conditions that would exclude them from safely receiving the treatments.

Inclusion Criteria

I have received at least one dose of an FDA-approved COVID-19 vaccine.

I am 70-74 years old and considered unfit or frail due to multiple health conditions.

I agree to either not have sex or use birth control, and not donate sperm during the trial.

Exclusion Criteria

I currently have an active infection.

Unable or unwilling to sign consent

I have had a stem cell transplant before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Mosunetuzumab and Polatuzumab Vedotin with split-dose CHP chemotherapy for up to six cycles

24 weeks

12 visits (in-person)

Interim Assessment

Interim response assessment with PET/CT and MRD testing to determine eligibility for abbreviated treatment

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Mosunetuzumab
• Polatuzumab Vedotin

Trial Overview

The study is testing if adding mosunetuzumab (Mosun) and polatuzumab vedotin (Pola) to a split-dose CHP chemotherapy regimen improves outcomes in these patients. It's a phase 2 study, meaning it focuses on the efficacy of this combination treatment.

How Is the Trial Designed?

Group I: Mosum-Pola-SD-CHP Experimental Treatment 6 Interventions

Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

Polatuzumab vedotin, when combined with bendamustine and rituximab (polatuzumab-BR), is an effective treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), offering a new therapeutic avenue for those who do not respond to standard treatments.

This combination therapy is considered safe and is particularly beneficial for transplant-ineligible patients, with ongoing trials exploring its use alongside other treatments like CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. Walji, M., Assouline, S.[2021]

Polatuzumab vedotin is an approved treatment for relapsed or refractory diffuse large B-cell lymphoma, specifically targeting the CD79b protein on B cells.

The drug works by delivering a cytotoxic molecule that inhibits tubulin polymerization, effectively killing the targeted cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin Approved for DLBCL. [2020]

Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells, delivering a cytotoxic agent (MMAE) to inhibit cell division and induce cell death, making it a promising treatment for certain blood cancers.

In June 2019, polatuzumab vedotin received accelerated FDA approval for use with bendamustine and rituximab in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and it is currently under review in the EU and in various stages of development for other related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: First Global Approval. Deeks, ED.[2023]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79B, is effective for treating relapsed/refractory diffuse large B-cell lymphoma when combined with bendamustine and rituximab.

Research by Kawasaki et al. suggests potential mechanisms of resistance to polatuzumab vedotin in lymphoma cells, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. Tarantelli, C., Bertoni, F.[2023]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

In a study of 70 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone), the treatment showed comparable outcomes in terms of time to progression and disease-specific survival when matched against a control group of 140 patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Although R-CEOP demonstrated similar progression-free and disease-specific survival rates, it was associated with a lower overall survival rate (30% vs 49% for R-CHOP), likely due to the higher comorbidities and frailty in the R-CEOP group, indicating that while R-CEOP is a viable alternative for patients who cannot tolerate anthracyclines, it may not be as effective overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. Moccia, AA., Schaff, K., Freeman, C., et al.[2021]

In a study of 326 lymphoma patients treated with Myocet® (a liposomal formulation of doxorubicin), the treatment showed a comparable response rate of at least 58% to conventional therapies, indicating its efficacy in managing lymphoproliferative disorders.

Despite a high prevalence of cardiovascular comorbidities (72% of patients), the incidence of severe cardiac events was relatively low, suggesting that Myocet® may have a better safety profile regarding cardiotoxicity compared to traditional doxorubicin formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in lymphoma: patterns of toxicity and outcome in a large observational trial. Wasle, I., Gamerith, G., Kocher, F., et al.[2018]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

In a study of 71 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) showed an overall response rate of 47.9%, with a complete response rate of 32.4% after a median of 3 treatment cycles.

The treatment demonstrated a manageable safety profile, with the most common severe side effects being grade 3-4 neutropenia and thrombocytopenia, indicating that Pola-BR is a promising and effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey. Dal, MS., Ulu, BU., Uzay, A., et al.[2023]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[2022]

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