Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma

Recruiting at 1 trial location

Overseen By Matthew Mei, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Anticancer agents

Disqualifiers: Active infection, 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: 51

Duration: 18-51 weeks

41 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic immunosuppressive therapy, it must be reduced to a low dose before starting the trial. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drugs Mosunetuzumab and Polatuzumab Vedotin for treating follicular lymphoma?

Polatuzumab Vedotin has shown significant activity in treating follicular lymphoma, as seen in trials where it was combined with other drugs like obinutuzumab and lenalidomide. Mosunetuzumab has been conditionally approved in the EU for treating relapsed or refractory follicular lymphoma, indicating its potential effectiveness. ^{1 2 3 4 5}

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

Polatuzumab Vedotin, also known as Polivy, has been studied in combination with other drugs for treating certain types of lymphoma, and it has shown a low risk of causing immune reactions in patients. It has been approved for use in some lymphoma treatments, indicating it is generally considered safe when used as directed. ^{1 4 6 7 8}

How is the drug combination of Mosunetuzumab and Polatuzumab Vedotin unique for treating follicular lymphoma?

This drug combination is unique because Mosunetuzumab is a bispecific antibody that engages T-cells to target cancer cells, while Polatuzumab Vedotin is an antibody-drug conjugate that delivers a toxic agent directly to B-cells. Together, they offer a novel approach by combining two different mechanisms to attack the cancer more effectively. ^{1 2 3 8 9}

What is the purpose of this trial?

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 after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Giving mosunetuzumab and polatuzumab vedotin may kill more cancer cells in patients with relapsed or refractory grade 1-3a follicular lymphoma.

Research Team

Matthew Mei, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with grade 1-3a follicular lymphoma that has either relapsed or hasn't responded to previous treatments. Participants should have a type of cancer that the drugs used in this study can target.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

I have recovered from side effects of previous cancer treatments.

Assent, when appropriate, will be obtained per institutional guidelines

Exclusion Criteria

I do not have active viral infections like HBV, HCV, HIV, or chronic EBV.

I have heart, liver, autoimmune conditions, or had major surgery recently.

I am not on any immune-suppressing drugs, with certain exceptions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive polatuzumab vedotin IV and mosunetuzumab SC in cycles every 21 days for up to 6-17 cycles

18-51 weeks

Visits every 21 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Follow-up at 30 days post-treatment and then for 3 years

Treatment Details

Interventions

• Mosunetuzumab
• Polatuzumab Vedotin

Trial Overview The effectiveness of mosunetuzumab and polatuzumab vedotin is being tested on patients with specific types of follicular lymphoma. The trial involves various diagnostic tests like CT, PET, MRI scans, and questionnaires to monitor progress.

Participant Groups

Group I: Treatment (mosunetuzumab, polatuzumab vedotin) Experimental Treatment 7 Interventions

Patients receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 8-17 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, PET/CT, or MRI throughout the study.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

The Pola-G-Len combination therapy demonstrated a high complete response rate of 63% and an overall objective response rate of 76% in patients with relapsed or refractory follicular lymphoma, indicating its potential efficacy in this challenging patient population.

The study identified a recommended phase 2 dose of 1.4 mg/kg polatuzumab vedotin plus 20 mg lenalidomide, with manageable safety profiles, although common adverse events included neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Diefenbach, C., Kahl, BS., McMillan, A., et al.[2022]

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 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]

In a study of 57 patients with relapsed large B-cell lymphoma after CAR T-cell therapy, polatuzumab vedotin (PV) showed a response rate of 44%, with 14% achieving complete remission, indicating its potential efficacy in this challenging patient population.

The median progression-free survival was only 10 weeks, and factors like bone marrow involvement and high lactate dehydrogenase levels were linked to shorter survival, highlighting the need for further research on treatment resistance and consolidation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. Gouni, S., Rosenthal, AC., Crombie, JL., 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]

The study evaluated the antibody-drug conjugate polatuzumab vedotin (pola) combined with rituximab/obinutuzumab and chemotherapy in treating B-cell non-Hodgkin lymphoma, showing that pola's pharmacokinetics were consistent and dose-proportional across different treatment cycles.

There were no significant drug-drug interactions between pola and the chemotherapy regimen (R/G-CHP), indicating that pola can be safely used in combination with these treatments for previously untreated diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Shemesh, CS., Agarwal, P., Lu, T., et al.[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]

In a study of 69 patients with aggressive B-cell lymphoma treated with polatuzumab vedotin combined with bendamustine and rituximab, a 50% response rate was observed, with a 24% complete response rate, indicating some efficacy in a real-world setting.

However, the median progression-free survival (PFS) was only 2.0 months, and survival was 5.3 months, which is lower than what was reported in clinical trials, particularly for patients with prior refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. Smith, SD., Lopedote, P., Samara, Y., et al.[2022]

References

1. 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]

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

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. [2022]

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

Mosunetuzumab: First Approval. [2022]

4. 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]

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

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]

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

Polatuzumab Vedotin: First Global Approval. [2023]

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

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. [2022]