Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma

Recruiting in Palo Alto (17 mi)

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II clinical trial studies the combination of mosunetuzumab and polatuzumab vedotin in order to see how well it works in patients with untreated follicular lymphoma. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead. Polatuzumab vedotin is an antibody-drug conjugate that attaches to certain cancerous B cells and then delivers a drug specifically to those cells.

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.

What data supports the effectiveness of the drug Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma?

Polatuzumab vedotin has shown effectiveness in treating diffuse large B-cell lymphoma, a type of blood cancer, especially when combined with other drugs like rituximab. This suggests it might also be effective in treating similar conditions like follicular lymphoma. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Polatuzumab Vedotin safe for humans?

The combination of Mosunetuzumab and Polatuzumab Vedotin has been studied in patients with relapsed or refractory large B cell lymphoma, showing a favorable safety profile. Common side effects included neutropenia (low white blood cell count) and fatigue, with some patients experiencing cytokine release syndrome (a reaction that can cause fever and low blood pressure). ^{1 5 6 7 8}

What makes the drug combination of Mosunetuzumab and Polatuzumab Vedotin unique for treating follicular lymphoma?

The combination of Mosunetuzumab and Polatuzumab Vedotin is unique because it targets two different components of B-cells: Mosunetuzumab targets CD20, while Polatuzumab Vedotin targets CD79b. This dual targeting approach may enhance the effectiveness of treatment by attacking the cancer cells from multiple angles. ^{1 2 8 9 10}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

One or more of the following criteria (adapted from GELF criteria): Any nodal or extranodal tumor mass with diameter > 7 cm, Involvement of at least 3 nodal sites, each with diameter > 3 cm, Presence of any systemic or B symptoms, Splenic enlargement with inferior margin below the umbilical line, Compression syndrome (e.g., ureteral, orbital, gastrointestinal), Pleural or peritoneal serous effusion (irrespective of cell content), Cytopenia(s) attributable to lymphoma, At least 18 years of age, ECOG performance status ≤ 2, Adequate hematologic and organ function (unless due to underlying lymphoma per the investigator; see below): Absolute neutrophil count ≥ 1,000/mcL, Platelets ≥ 75,000/mcL, Hemoglobin ≥ 8 g/dL, Serum total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with Gilbert syndrome), AST(SGOT)/ALT(SGPT) ≤ 3 x IULN, Serum creatinine ≤ 1.0 x IULN or creatinine clearance ≥ 50 mL/min by Cockcroft-Gault, Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled if the following criteria are met: Absolute neutrophil count ≥ 500/mcL, Platelet count ≥ 50,000/mcL without platelet transfusion within 14 days prior to the first dose of mosunetuzumab, Hemoglobin ≥ 7 g/dL without red blood cell transfusion within 7 days prior to the first dose of mosunetuzumab, Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

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.

Trial Timeline

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

Treatment Details

Interventions

• Mosunetuzumab (Monoclonal Antibodies)
• Polatuzumab vedotin (Monoclonal Antibodies)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University School of Medicine Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2027

Patients Recruited

2,353,000+

Genentech, Inc.

Industry Sponsor

Trials

1578

Patients Recruited

569,000+

Institute for Follicular Lymphoma

Collaborator

Trials

1

Patients Recruited

30+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2018]

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

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. [2023]

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

Polatuzumab Vedotin: First Global Approval. [2023]

9. New Zealand 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. [2022]

10. England 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. [2021]