Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma

Not currently recruiting at 1 trial location

Overseen By Nancy L. Bartlett

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Anti-CD20 antibodies

Disqualifiers: Aggressive B cell lymphoma, CNS disease, Autoimmune 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: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, mosunetuzumab and polatuzumab vedotin, to evaluate their effectiveness in treating follicular lymphoma, a type of blood cancer. Mosunetuzumab helps the immune system destroy cancer cells, while polatuzumab vedotin (also known as Polivy) targets and delivers medicine directly to these cells. Suitable candidates for this trial have follicular lymphoma with specific symptoms, such as large tumors or multiple affected lymph nodes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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, you cannot participate if you have been on certain immunosuppressive medications within 2 weeks before starting the trial. 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 people. Studies have found that most patients can handle the side effects, which are usually mild.

In earlier research, these drugs were given to patients whose follicular lymphoma had returned. The treatment showed promising results, with few serious side effects. Common side effects included low blood cell counts and tiredness, but these were usually not severe.

Overall, the safety data suggests that this combination is reasonably safe for patients. Participants in these studies experienced long-lasting positive responses, indicating the treatment worked well for an extended period. This is encouraging for those considering joining a clinical trial with these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mosunetuzumab and polatuzumab vedotin for follicular lymphoma because these treatments offer a unique approach compared to current standard options like rituximab and chemotherapy. Mosunetuzumab is a bispecific antibody that targets CD3 and CD20, engaging the body's T-cells to attack cancer cells directly, which is different from traditional chemotherapy. Polatuzumab vedotin, on the other hand, is an antibody-drug conjugate targeting CD79b, delivering a toxic payload directly to the cancer cells, minimizing damage to healthy cells. This combination aims to enhance treatment efficacy while potentially reducing side effects, providing new hope for patients with follicular lymphoma.

What evidence suggests that this combination treatment could be effective for follicular lymphoma?

Research has shown that the combination of mosunetuzumab and polatuzumab vedotin, which participants in this trial will receive, holds promise for treating follicular lymphoma. These drugs work synergistically to combat cancer. Mosunetuzumab aids the immune system by linking T cells (a type of immune cell) to cancer cells, facilitating their destruction. Polatuzumab vedotin delivers medicine directly to cancer cells to inhibit their growth. Together, they have effectively reduced the risk of disease progression or death in patients with certain types of lymphoma. Early clinical data shows strong anti-lymphoma effects and manageable side effects. ^{1 2 4 5 6}

Who Is on the Research Team?

David Russler-Germain, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults diagnosed with untreated follicular lymphoma grades 1-3A, stages II-IV. Participants must have certain symptoms or tumor sizes, be in good physical condition (ECOG ≤2), and have adequate organ function. They should not have had prior treatments for this lymphoma or other recent immunotherapies, CNS diseases, severe allergies to monoclonal antibodies, active infections like hepatitis B/C or HIV, autoimmune diseases requiring treatment, or any serious medical conditions that could interfere with the trial.

Inclusion Criteria

I have been diagnosed with a type of lymphoma that is not the most aggressive form.

Exclusion Criteria

Prior history of aggressive B cell lymphoma such as diffuse large B cell lymphoma or high-grade B cell lymphoma, Known history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, Known history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH), Current or past history of CNS lymphoma, Any prior systemic therapy for follicular lymphoma, Treatment with radiotherapy within 2 weeks prior to the first dose of mosunetuzumab (otherwise one measurable lesion outside of the radiation field must remain), Treatment with any anti-CD20 monoclonal antibody within 4 weeks of Day 1 of Cycle 1, Current or recent history (within the last 6 months) of CNS disease, Treatment with systemic immunosuppressive medications, History of solid organ transplantation, History of allogeneic stem cell transplantation, Prior treatment with chimeric antigen receptor T cell therapy within 30 days before Day 1 of Cycle 1, History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies (mAbs), Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab formulation, History of erythema multiforme, Grade ≥ 3 rash, or blistering following prior treatment with immunomodulatory derivatives, Known active bacterial, viral, fungal, or other infection, Known or suspected chronic active Epstein-Barr virus (EBV) infection, Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease, Active hepatitis B infection, Active hepatitis C infection, Known history of human immunodeficiency virus (HIV) positive status, History of progressive multifocal leukoencephalopathy (PML), Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study, Other malignancy that could affect compliance with the protocol or interpretation of results, Active autoimmune disease requiring treatment, Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study, Pregnant or lactating or intending to become pregnant during the study, Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.

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 for 6 cycles, followed by mosunetuzumab alone for 2 additional cycles

24 weeks

Mosunetuzumab on Days 1, 8, and 15 of cycle 1, then Day 1 thereafter; Polatuzumab vedotin on Day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extension

Participants with partial response or stable disease may receive up to 9 additional cycles of mosunetuzumab

27 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Polatuzumab vedotin

Trial Overview

The trial is testing a combination of two drugs: Mosunetuzumab and Polatuzumab vedotin on patients who haven't been treated before for follicular lymphoma. Mosunetuzumab directs immune cells to attack cancerous cells while Polatuzumab delivers a drug directly to them.

How Is the Trial Designed?

Group I: Mosunetuzumab and Polatuzumab Vedotin Experimental Treatment 2 Interventions

Patients receive CD3xCD20 bispecific antibody mosunetuzumab administered subcutaneously in combination with CD79b directed ADC polatuzumab vedotin administered intravenously. Mosunetuzumab and polatuzumab vedotin are given in combination for 6 cycles. Mosunetuzumab is given on Days 1, 8, and 15 of cycle 1 and then Day 1 thereafter, and polatuzumab vedotin is given on Day 1. After 6 cycles, patients continue on mosunetuzumab alone for 2 additional cycles. Patients undergo scans at the end of cycle 8, and if those scans show a complete response, patients will stop any further treatment and will enter follow-up. Patients with a partial response or stable disease on scans at the end of cycle 8 may receive up to 9 additional cycles of mosunetuzumab in the absence of disease progression or unacceptable toxicity. All cycles are planned to be 21 days.

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Institute for Follicular Lymphoma

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., 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]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

Polatuzumab vedotin, an antibody-drug conjugate for non-Hodgkin's lymphoma, demonstrated similar binding affinity and anti-tumor activity in both human and cynomolgus monkey models, supporting its potential efficacy in humans.

The surrogate ADC used in the study effectively mimicked the pharmacological effects of polatuzumab vedotin, showing B-cell depletion and similar toxicity profiles, which validated its use for preclinical evaluations before human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation and use of an anti-cynomolgus monkey CD79b surrogate antibody-drug conjugate to enable clinical development of polatuzumab vedotin. Li, D., Lee, D., Dere, RC., et al.[2021]

Polatuzumab vedotin, an antibody-drug conjugate, demonstrated an acceptable safety profile in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), with a recommended phase 2 dose of 2.4 mg/kg showing objective responses in 23 out of 42 evaluable patients.

In contrast, the treatment was not effective for patients with chronic lymphocytic leukaemia (CLL), as no objective responses were observed, highlighting the need for further assessment of polatuzumab vedotin specifically in NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Palanca-Wessels, MC., Czuczman, M., Salles, G., et al.[2018]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, shows promise in treating relapsed or refractory B-cell non-Hodgkin lymphomas, particularly when combined with rituximab and bendamustine, as indicated by early clinical data.

The ongoing phase III POLARIX trial is exploring its effectiveness in first-line treatment for untreated patients, with careful management of dosing to minimize the risk of peripheral neuropathy, potentially making it a key player in DLBCL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma. Bourbon, E., Salles, G.[2022]

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, 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 phase 1b/2 trial involving 120 patients with relapsed/refractory aggressive large B cell lymphoma, the combination of mosunetuzumab and polatuzumab vedotin achieved a high overall response rate of 59.2% and a complete response rate of 45.9%, indicating strong efficacy as a second-line therapy.

The treatment demonstrated a favorable safety profile, with the most common serious side effects being neutropenia (25%) and fatigue (6.7%), and only 16.7% of patients experiencing any-grade cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Budde, LE., Olszewski, AJ., Assouline, S., et al.[2023]

Polatuzumab vedotin (POLIVY®) is an effective treatment for adult patients with diffuse large B-cell lymphoma, approved after showing significant anti-cancer activity by delivering a potent drug directly to B cells.

The incidence of anti-drug antibodies (ADA) against polatuzumab vedotin is low, likely due to its mechanism of action that targets and kills B cells, which minimizes immune response and supports a favorable benefit/risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Dere, RC., Beardsley, RL., Lu, D., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06453044

Study Details | NCT06453044 | Mosunetuzumab and ...

This phase II trial tests how well mosunetuzumab and polatuzumab vedotin works in treating patients with grade 1-3a follicular lymphoma that has come back ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05169658

Study Details | NCT05169658 | Mosunetuzumab With or ...

Giving mosunetuzumab with polatuzumab vedotin and obinutuzumab may work better in treating patients with untreated indolent B-cell non-Hodgkin lymphoma.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10803244/

Mosunetuzumab with polatuzumab vedotin in relapsed or ...

Mosunetuzumab and polatuzumab vedotin have individually shown promising anti-lymphoma activity and manageable toxicity profiles in patients with R/R NHL.

4.

ash.confex.com

ash.confex.com/ash/2024/webprogram/Paper202085.html

4414 Mosunetuzumab Plus Polatuzumab Vedotin Induces ...

A phase 1/2 study of Mosun plus Pola in r/r B cell lymphoma showed promising efficacy and a reasonable safety profile (Budde Nat Med 2024).

5.

onclive.com

onclive.com/view/mosunetuzumab-plus-polatuzumab-vedotin-triples-median-pfs-in-transplant-ineligible-lbcl

Mosunetuzumab Plus Polatuzumab Vedotin Triples ...

Mosunetuzumab-axgb (Lunsumio) plus polatuzumab vedotin-piiq (Polivy; Mosun-Pola) reduced the risk of disease progression or death by 59%, ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02257567

NCT02257567 | A Study of Polatuzumab Vedotin ...

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of ...